Of known structures (60-80% of genes) how many are multidomain proteins?
Different combinations of domains are advantageous because they allow the organism to specialise
How can we recognize domains?
Amino acid sequencing
Why are DNA/amino acid sequencing of little use when investigating relationships between proteins?
As diversion occurs, sequence patterns are lost even as the fold remains the same
They can detect short evolutionary relationships only
The techniques for reading the sequences are unreliable
Identical sequences can give different aa sequences/folds
When investigating using structure, how do we identify domains?
Amino acid sequence
Domains have the same fold
The interaction of the protein with other proteins
There is a limited number of folds in nature (10^3-4)
Structural similarity occurs from what kind of evolution?
Sequence is more highly conserved than protein structure
Define convergent evolution
The independent evolution of similar features in different lineages
The carrying of a feature from a common ancestor into two lines, which allows the reconvergence of the two lines into a single species again
The dependent evolution of similar features in two species that interact/co-operate closely
How does the CATH system establish taxonomy?
Cut proteins into domains and use computor analysis to group domains
Uses structure based analysis
Which of the following classifications would be in the Class portion of the CATH system
Connectivity of fold
Which of the following would be in the Architecture domain of the CATH system
Two layer sandwitch
Put the following in order of their use in the CATH system
B- Sequence Superfamily
C- Homologous Superfamily
There are 3 classes, 32 architectures and 820 topologies in the CATH system
The SCOP classifications, in descending order, are Class-Superfamily-Family-Fold-Species
What is the specification after Superfamiy in the Pfam system?
All the systems agree in _% of cases
To be homologous, two proteins must have two of which of the following in common?
What is the following describing- a protein contained in two different species with a similar function due to divergent evolution
What is the following describing- changes to a sequence following gene duplication leads to a variant copy with an additional (usually similar) function in the same species
Give the two defining features of orthologues
RMSD of >4
SI may be high or low
NAD is a co-enzyme found in all living cells that accepts and donates electrons
NAD is made of three nucleotides and a phosphate group
Which of the following binds NAD when present in a protein?
A Rossman Fold
A Sherman Fold
A Fieldman Fold
The Rossman Fold has it's 6 beta sheets arranged in what order?
In a Rossman fold, the crossover of the strands form the binding site
In lactate dehydrogenase, which terminal domain contains the Rossman fold?
What is the role of the C-terminal domain in dehydrogenases?
Enzyme catalytic activity
Lactate dehydrogenase catalyses lactate --> oxaloacetate
Malate dehydrogenase is structually identical to LADH, so why do they have different substrates?
An SI of 17%
They operate in cells where only one or the other is avalible
Lactate and malate are structurally identical, but have different components
How can we tell two proteins are not homologues?
They have a different function
They have a different S.I
They're found in different species
They're structurally different
What is the following descrbing- the existence of a shared ancestry between two structures (in this case proteins)
Alcohol dehydrogenase contains a Rossman fold
ADH and LDH have an RMSD of 2.2 & an S.I of 17%- what relationship do they share?
In the case of sequence diversity between proteins, surface residues change less than core/functional site residues
Where do residue insertions usually occur?
In the functional site
In loops connecting secondary structures
In alpha helices
The functional diversity of a domain superfamily depends on the fold