Protein evolution

Description

Protein Form and Function Mind Map on Protein evolution, created by sophie_connor on 26/05/2013.
sophie_connor
Mind Map by sophie_connor, updated more than 1 year ago
sophie_connor
Created by sophie_connor over 11 years ago
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Resource summary

Protein evolution
  1. Levels of protein structure
    1. Primary
      1. Proteins with a similar primary structure have a similar tertiary structure
      2. Secondary
        1. Supersecondary structure
          1. Helix-loop helix
            1. Coiled coil
              1. Helix bundle
                1. BaB unit
                  1. Hairpin
                    1. B meander
                      1. Greek key
                        1. B sandwich
                      2. Tertiary
                        1. Domains
                          1. Independent folding units
                            1. Have specific functions
                              1. Hydrophobic interactions are the major driving force for folding domains
                                1. Building blocks of proteins
                                  1. Recombine with different partners to carry out different functions
                                    1. Important because
                                      1. They're basic evolutionary units
                                        1. Provide function
                                          1. Recombine with other proteins to perform different functions
                                          2. How to recognise domains?
                                            1. DNA sequence
                                              1. Pairs of closely related proteins have similar DNA sequences
                                                1. Useful for short evolutionary distances
                                                2. Amino acid sequence
                                                  1. Domains have similar amino acid sequences
                                                    1. Sequence pattern is lost as they diverge
                                                    2. Protein structure
                                                      1. Domains have the same fold
                                                        1. Domains are independently folding units
                                                      2. Folds
                                                        1. Each domain has a specific topolgy/fold
                                                          1. There are limited number of folds in nature
                                                          2. Classification
                                                            1. Taxonomy
                                                              1. Evolution conserved structure because structure determines function
                                                                1. Classification systems
                                                                  1. CATH
                                                                    1. Chop proteins into domains
                                                                      1. Use sequence and structural analysis programs to group domains into evolutionary and structural families
                                                                      2. Classes
                                                                        1. What is the major secondary structure
                                                                        2. Architecture
                                                                          1. Describes shape of fold
                                                                            1. Rossman fold
                                                                              1. An NAD binding domain
                                                                                1. NAD
                                                                                  1. Cofactor that reversibly accepts a hydride ion
                                                                                    1. Ion is lost or gained by substrate in redox reaction
                                                                                    2. Consists of 2 nucleotides joined a phosphate group
                                                                                      1. One nucleotide contains an adenine base and the other nicotinamide
                                                                                  2. One of the most ubiquitous domains
                                                                                    1. Rossman domain binds nicotinamide adenine dinucleotide (NAD+)
                                                                                      1. Rossman domains have alpha/beta fold, central beta sheet with 5 alpha helices surrounding it
                                                                                        1. Example
                                                                                          1. Lactate dehydrogenase
                                                                                            1. Metabolic enzyme
                                                                                              1. Catalyses conversion of L-lactate to pyruvate
                                                                                                1. Last step in anaerobic glycolysis
                                                                                                2. N-terminal domain is NAD binding domain/Rossman fold
                                                                                                  1. C-terminal domain
                                                                                                    1. Catalytic domain
                                                                                                      1. For substrate specificity and precise reaction of enzyme
                                                                                                      2. Specific to lactate/malate dehydrogenases
                                                                                                    2. Malate dehydrogenase
                                                                                                      1. Catalyses conversion of malate to oxaloacetate
                                                                                                        1. N-terminal domain is NAD binding/Rossman fold
                                                                                                          1. C-terminal domain is catalytic domain
                                                                                                          2. LDH and MDH
                                                                                                            1. Structure is conserved more than sequence
                                                                                                              1. 17% sequence identity
                                                                                                                1. Function of NAD binding domain conserved
                                                                                                                  1. Change in sequence binding domain enables change of substrate specificity in catalytic domain
                                                                                                                  2. Alcohol dehydrogenase
                                                                                                                    1. Catalyses oxidation of ethanol to acetylaldehyde
                                                                                                            2. Topology
                                                                                                              1. Describes connectivity of fold
                                                                                                              2. Homologous superfamily
                                                                                                                1. Is there enough evidence to say the domains came from the same superfamily
                                                                                                              3. SCOP
                                                                                                                1. Structural Classification Of Proteins
                                                                                                                  1. Class, fold, superfamily, species
                                                                                                                    1. Structure based
                                                                                                                    2. Pfam
                                                                                                                      1. Protein family database
                                                                                                                        1. Superfamily, clade
                                                                                                                        2. Vary in domain definitions
                                                                                                                  2. Quaternary
                                                                                                                  3. Proteins are stabilised by non-bonded interactions
                                                                                                                    1. Electrostatic interactions
                                                                                                                      1. Hydrogen bonds
                                                                                                                        1. Hydrophobic interactions
                                                                                                                          1. Van der Waals
                                                                                                                          2. How can you tell if two proteins are similar?
                                                                                                                            1. Amino acid sequence
                                                                                                                              1. Sequence identity = number of identical/number of residues aligned x 100
                                                                                                                              2. Measure protein structure directly
                                                                                                                                1. Superposition of protein structures
                                                                                                                                  1. Proteins on an axis
                                                                                                                                    1. Superimpose one on the other
                                                                                                                                2. Scoring structural similarity
                                                                                                                                  1. Root mean square deviation (RMSD)
                                                                                                                                    1. Make an alignment- either using sequence or structural methods
                                                                                                                                      1. For each pair of aligned residues use C-alphas
                                                                                                                                        1. Calculate how far apart they are
                                                                                                                                          1. Sum this value for all residues
                                                                                                                                            1. Divide by number of residues
                                                                                                                                  2. Reasons for structural similarity
                                                                                                                                    1. Divergent evolution from a common ancestor
                                                                                                                                      1. Structure is more highly conserved than sequence
                                                                                                                                      2. Convergent evolution
                                                                                                                                        1. Limited number of ways of packing helices and strands in 3D space
                                                                                                                                    2. Homology
                                                                                                                                      1. Implies evolutionary relationship
                                                                                                                                        1. Genes (proteins) either are or aren't
                                                                                                                                          1. Orthologs
                                                                                                                                            1. Common ancestor
                                                                                                                                              1. Speciation
                                                                                                                                                1. Different species
                                                                                                                                                  1. Same or highly similar function
                                                                                                                                                  2. Paralogs
                                                                                                                                                    1. Common ancestor
                                                                                                                                                      1. Gene duplication
                                                                                                                                                        1. Same or different species
                                                                                                                                                          1. Different but related function
                                                                                                                                                          2. Identifying homologues
                                                                                                                                                            1. Significant structural simialarity
                                                                                                                                                              1. Significant sequence similarity
                                                                                                                                                                1. Functional similarity
                                                                                                                                                                2. Example
                                                                                                                                                                  1. Cholera toxin and Heat labile enterotoxin
                                                                                                                                                                  2. Analogous structures
                                                                                                                                                                    1. Structural similarity
                                                                                                                                                                      1. No sequence or functional similarity
                                                                                                                                                                        1. Example
                                                                                                                                                                          1. Heat labile enterotoxin and staphylococcal nuclease
                                                                                                                                                                      2. Homologous domain superfamilies
                                                                                                                                                                        1. Sequence diversity
                                                                                                                                                                          1. Different evolutionary constraints in different positions in the protein structure
                                                                                                                                                                            1. Core residues are more highly conserved
                                                                                                                                                                              1. Critical for folding and stability
                                                                                                                                                                              2. Functional residues highly conserved
                                                                                                                                                                                1. Residues for enzyme function or protein-protein interactions
                                                                                                                                                                                2. Surface residues are least conserved
                                                                                                                                                                                  1. Can accommodate small insertions and deletions
                                                                                                                                                                                3. Structural diversity
                                                                                                                                                                                  1. Core is usually highly convserved
                                                                                                                                                                                    1. Residue insertions occur in the loops connecting secondary structures
                                                                                                                                                                                      1. Residue substitutions can cause shifts in the orientations of secondary structure
                                                                                                                                                                                      2. Functional diversity
                                                                                                                                                                                        1. Dependent on fold
                                                                                                                                                                                          1. Some folds can support a large variety of similar functions
                                                                                                                                                                                            1. Some folds have a limited selection of functions
                                                                                                                                                                                              1. 1 amino acid can change the function of a protein
                                                                                                                                                                                                1. Proteins can share <10% sequence identity but have identical functions in different organisms
                                                                                                                                                                                                  1. What is function?
                                                                                                                                                                                                    1. Biochemical function
                                                                                                                                                                                                      1. Is chemistry conserved?
                                                                                                                                                                                                        1. Is substrate conserved?
                                                                                                                                                                                                          1. Is product conserved?
                                                                                                                                                                                                          2. Is cell localisation convserved?
                                                                                                                                                                                                            1. Several ideas have been developed to capture function
                                                                                                                                                                                                              1. Enzyme classification system
                                                                                                                                                                                                                1. GO terms
                                                                                                                                                                                                          3. Methods for recognising domains uses CATH database
                                                                                                                                                                                                            1. Algorithms for recognising domain boundaries
                                                                                                                                                                                                              1. Detective
                                                                                                                                                                                                                1. Each domain should have a recognisable hydrophobic core
                                                                                                                                                                                                                2. Domak
                                                                                                                                                                                                                  1. Residues comprising a domain make more internal contacts than external ones
                                                                                                                                                                                                                  2. PUU
                                                                                                                                                                                                                    1. Computer program for protein folding units
                                                                                                                                                                                                                      1. Finds what interacts most and least with domains
                                                                                                                                                                                                                    2. Sequence methods for detecting protein domain homologues
                                                                                                                                                                                                                      1. Scan sequence against profiles if sequence identity <35%
                                                                                                                                                                                                                      2. Structural methods
                                                                                                                                                                                                                        1. Distance matrices and contact maps
                                                                                                                                                                                                                          1. Describes the points of contact between residues in a protein
                                                                                                                                                                                                                        2. Challenges in comparing protein structures
                                                                                                                                                                                                                          1. Insertions or deletions of residues- usually not in secondary structures but in connecting loops
                                                                                                                                                                                                                            1. Ignore variable loop regions and only compare secondary structures
                                                                                                                                                                                                                              1. Use algorithms which can handle insertions/deletions
                                                                                                                                                                                                                              2. Structures are highly conserved
                                                                                                                                                                                                                                1. Structure is more conserved than sequence
                                                                                                                                                                                                                                  1. Considerable differences between structure outside the core
                                                                                                                                                                                                                                2. Use literature
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