Structure, function and evolution of multidomain proteins

Christine Vogel, Matthew Bashton, Nicola D Kerrison, Cyrus Chothia and Sarah
A Teichmann

Current Opinion in Structural Biology 2004, 14:208-216

Proteins are composed of evolutionary units called domains; the majority of
proteins consist of at least two domains. These domains and nature of their
interactions determine the function of the protein. The roles that
combinations of domains play in the formation of the protein repertoire have
been found by analysis of domain assignments to genome sequences. Additional
findings on the geometry of domains have been gained from examination of
three-dimensional protein structures. Future work will require a
domain-centric functional classification scheme and efforts to determine
structures of domain combinations.

Introduction

There are various uses of the word domain with respect to proteins. Here, we
define a protein domain as an independent, evolutionary unit that can form a
single-domain protein or be part of one or more different multidomain
proteins. The domain can either have an independent function or contribute
to the function of a multidomain protein in cooperation with other domains.
The definition of a domain as an evolutionary unit is used in the Structural
Classification of Proteins (SCOP) database [1].

In SCOP, domains that have a common ancestor based on sequence, structural
and functional evidence are grouped into superfamilies. There are more than
1200 domain superfamilies in the current version of the database [2], though
estimates of the total number of superfamilies vary from a few to several
thousand [3-5] . Domains from the superfamilies in SCOP can be assigned to
40-60% of the residues in the proteins of completely sequenced genomes using
homology-based methods. These include the profile hidden Markov models in
the SUPERFAMILY database [6,7.] , the structural profiles of the PSSM server
[8], the PSI-BLAST profiles in the Gene3D database [9] or combined
approaches [10.]. From the assignment of structural domains to genome
sequences, it is clear that some two-thirds of proteins consist of two or
more domains in prokaryotes [11] and an even larger fraction in eukaryotes
[12].

As most proteins consist of multiple domains, and domains determine the
function and evolutionary relationships of proteins, it is important to
understand the principles of domain combinations and interactions. In this
review, we discuss how domain superfamilies form the repertoire of
multidomain proteins via duplication and recombination ( Figure 1). We then
describe the principles and extent of conservation of the N- to C-terminal
order of domains, their three-dimensional geometry and their functional
relationships. This will illustrate the importance of domain combinations to
an understanding of protein evolution, structure and function, and to target
selection in structural genomics.

Read the rest at BioMedNet
http://gateways.bmn.com/magazine/article?pii=S0959440X04000454

Posted by
Robert Karl Stonjek
(Now Moderator of the Evolutionary Psychology Group -
http://groups.yahoo.com/group/evolutionary-psychology )
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