Module 2: V10 - V12 Flashcards
What is a subunit?
a polypeptide chain
What is the primary structure of a protein?
the amino acid sequence
What is the secondary structure of a protein?
the elements, ɑ-helices, β-sheets and turns (also simple motifs ɑ-ɑ, β-β, β-ɑ-β which are supersecondary structures)
What is the tertiary structure of a protein?
the overall spatial arrangement of atoms in a protein i.e. describes the fold of a protein chain/subunit (domains/folds/modules and arrangement of domains)
How is the tertiary structure of a protein stabilised?
stabilised by numerous weak interactions between amino acid side chains (e.g. hydrophobic and polar interactions + disulfide bonds)
How is a quaternary structure formed?
by the assembly of individual polypeptides into a larger functional cluster
i.e. the arrangement of two or more protein subunits
What is a domain?
a region within the native tertiary structure for which evidence can be provided of an existence independent of the rest of the protein (fold independently)
a single protein chain can consist of one or more domains
What is a fold?
defined by the arrangement of secondary structure elements relative to each other in space
What is a module?
protein domains which have one or more repeating folds within their overall structure
What do modules do?
they can attribute a function to individual folds: catalytic, lipid-binding, peptide-binding, DNA binding, fibronectin-binding, transmembrane, etc.
How are new proteins with new functions made?
by mixing domains and mutating existing domains
What is intragenic mutation?
point mutations, insertions and deletions
What is gene duplication?
duplication a whole genome or part of a genome
What is DNA segment shuffle?
when two or more existing genes are broken and recombined
What is lateral gene transfer?
when one organism acquires parts of the genome of another
Can a domain be defined as an evolutionary unit or a structural unit?
an evolutionary unit
How do new proteins evolve?
by gene duplication and domain shuffling
Are new domains ever being created?
no, new domains are only ever being modified and readjusted as they are subjected to point mutations, insertions and deletions (change, gain and loss of function)
How are sequences of protein domains compared?
they are compared based on identity or similarity
What is meant by identity?
means exactly the same residue (invariant)
What is meant by similar?
means a change to a residue that is observed frequently or with similar physical-chemical properties e.g. Ser to Thr, Val to Leu (conservative)
How can alignments be improved? What does realignment account for?
by introducing gaps that account for residue insertions and deletions
How do the structures of proteins that are related by evolutionary events such as gene duplication, but have different sequences, compare?
each sequence “change” results in a small change to structure, however, structure changes much more slowly than sequence which means that for two proteins whose sequences show >25% identity they will have similar structure
What will gaps between two sequences result in?
a loop insertion within the general structural fold
What are homologues?
protein domains that have sequences which show >25% identity (similar ancestry/they have the same fold)
What are the two groups of homologues?
orthologues and paralogues
What are orthologues?
homologous proteins that perform the same function in different species e.g. horse and tuna trypsin
What are paralogues?
homologous proteins that perform different but related functions within one organism e.g. human trypsin, compared with human thrombin
What does it mean if sequence identity is low «25% and the proteins are functionally different?
it is hard to draw conclusions
if we find the fold to be similar then they are likely to be homologues
Define the term “protein domain” in terms of folding and structure.
the term “protein domain” refers to a region within the native tertiary structure which folds independently of the rest of the protein
Antibodies are Y-shaped heterotetramers composed of two light chains and two heavy chains. Discuss the secondary, tertiary and quaternary structure of antibodies.
secondary structures = ɑ-helices, β-sheets, turns and simple motifs (ɑ-ɑ, β-β, β-ɑ-β)
tertiary structures = individual light chain and heavy chain segments which would fold independently of one another + be consisted of different unique polypeptide chains
quaternary structure = assembly of the heavy and light chains into a functional protein
What are four genetic mechanisms that can give rise to new proteins with new functions?
intragenic mutation, gene duplication, DNA segment shuffle and lateral gene transfer
What is the difference between sequence identity and sequence similarity? Give an example of similarity.
sequence identity means that the residues are exactly the same while sequence similarity means a change to a residue that is observed frequently or with similar physical-chemical properties e.g. Ser to Thr, Val to Leu
The amino acid sequences of two different enzymes from two different species have 30% sequence identity. What can you safely say about these two proteins?
that they are homologues and have similar ancestry/are folded in a similar manner
