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109602
Protein evolution
Descrição
Protein Form and Function Mapa Mental sobre Protein evolution, criado por sophie_connor em 26-05-2013.
Sem etiquetas
protein form and function
protein form and function
Mapa Mental por
sophie_connor
, atualizado more than 1 year ago
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Criado por
sophie_connor
aproximadamente 11 anos atrás
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Resumo de Recurso
Protein evolution
Levels of protein structure
Primary
Proteins with a similar primary structure have a similar tertiary structure
Secondary
Supersecondary structure
Helix-loop helix
Coiled coil
Helix bundle
BaB unit
Hairpin
B meander
Greek key
B sandwich
Tertiary
Domains
Independent folding units
Have specific functions
Hydrophobic interactions are the major driving force for folding domains
Building blocks of proteins
Recombine with different partners to carry out different functions
Important because
They're basic evolutionary units
Provide function
Recombine with other proteins to perform different functions
How to recognise domains?
DNA sequence
Pairs of closely related proteins have similar DNA sequences
Useful for short evolutionary distances
Amino acid sequence
Domains have similar amino acid sequences
Sequence pattern is lost as they diverge
Protein structure
Domains have the same fold
Domains are independently folding units
Folds
Each domain has a specific topolgy/fold
There are limited number of folds in nature
Classification
Taxonomy
Evolution conserved structure because structure determines function
Classification systems
CATH
Chop proteins into domains
Use sequence and structural analysis programs to group domains into evolutionary and structural families
Classes
What is the major secondary structure
Architecture
Describes shape of fold
Rossman fold
An NAD binding domain
NAD
Cofactor that reversibly accepts a hydride ion
Ion is lost or gained by substrate in redox reaction
Consists of 2 nucleotides joined a phosphate group
One nucleotide contains an adenine base and the other nicotinamide
One of the most ubiquitous domains
Rossman domain binds nicotinamide adenine dinucleotide (NAD+)
Rossman domains have alpha/beta fold, central beta sheet with 5 alpha helices surrounding it
Example
Lactate dehydrogenase
Metabolic enzyme
Catalyses conversion of L-lactate to pyruvate
Last step in anaerobic glycolysis
N-terminal domain is NAD binding domain/Rossman fold
C-terminal domain
Catalytic domain
For substrate specificity and precise reaction of enzyme
Specific to lactate/malate dehydrogenases
Malate dehydrogenase
Catalyses conversion of malate to oxaloacetate
N-terminal domain is NAD binding/Rossman fold
C-terminal domain is catalytic domain
LDH and MDH
Structure is conserved more than sequence
17% sequence identity
Function of NAD binding domain conserved
Change in sequence binding domain enables change of substrate specificity in catalytic domain
Alcohol dehydrogenase
Catalyses oxidation of ethanol to acetylaldehyde
Topology
Describes connectivity of fold
Homologous superfamily
Is there enough evidence to say the domains came from the same superfamily
SCOP
Structural Classification Of Proteins
Class, fold, superfamily, species
Structure based
Pfam
Protein family database
Superfamily, clade
Vary in domain definitions
Quaternary
Proteins are stabilised by non-bonded interactions
Electrostatic interactions
Hydrogen bonds
Hydrophobic interactions
Van der Waals
How can you tell if two proteins are similar?
Amino acid sequence
Sequence identity = number of identical/number of residues aligned x 100
Measure protein structure directly
Superposition of protein structures
Proteins on an axis
Superimpose one on the other
Scoring structural similarity
Root mean square deviation (RMSD)
Make an alignment- either using sequence or structural methods
For each pair of aligned residues use C-alphas
Calculate how far apart they are
Sum this value for all residues
Divide by number of residues
Reasons for structural similarity
Divergent evolution from a common ancestor
Structure is more highly conserved than sequence
Convergent evolution
Limited number of ways of packing helices and strands in 3D space
Homology
Implies evolutionary relationship
Genes (proteins) either are or aren't
Orthologs
Common ancestor
Speciation
Different species
Same or highly similar function
Paralogs
Common ancestor
Gene duplication
Same or different species
Different but related function
Identifying homologues
Significant structural simialarity
Significant sequence similarity
Functional similarity
Example
Cholera toxin and Heat labile enterotoxin
Analogous structures
Structural similarity
No sequence or functional similarity
Example
Heat labile enterotoxin and staphylococcal nuclease
Homologous domain superfamilies
Sequence diversity
Different evolutionary constraints in different positions in the protein structure
Core residues are more highly conserved
Critical for folding and stability
Functional residues highly conserved
Residues for enzyme function or protein-protein interactions
Surface residues are least conserved
Can accommodate small insertions and deletions
Structural diversity
Core is usually highly convserved
Residue insertions occur in the loops connecting secondary structures
Residue substitutions can cause shifts in the orientations of secondary structure
Functional diversity
Dependent on fold
Some folds can support a large variety of similar functions
Some folds have a limited selection of functions
1 amino acid can change the function of a protein
Proteins can share <10% sequence identity but have identical functions in different organisms
What is function?
Biochemical function
Is chemistry conserved?
Is substrate conserved?
Is product conserved?
Is cell localisation convserved?
Several ideas have been developed to capture function
Enzyme classification system
GO terms
Methods for recognising domains uses CATH database
Algorithms for recognising domain boundaries
Detective
Each domain should have a recognisable hydrophobic core
Domak
Residues comprising a domain make more internal contacts than external ones
PUU
Computer program for protein folding units
Finds what interacts most and least with domains
Sequence methods for detecting protein domain homologues
Scan sequence against profiles if sequence identity <35%
Structural methods
Distance matrices and contact maps
Describes the points of contact between residues in a protein
Challenges in comparing protein structures
Insertions or deletions of residues- usually not in secondary structures but in connecting loops
Ignore variable loop regions and only compare secondary structures
Use algorithms which can handle insertions/deletions
Structures are highly conserved
Structure is more conserved than sequence
Considerable differences between structure outside the core
Use literature
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