An Isaac Newton Institute Workshop

Protein-Protein Interactions in Vitro and in Vivo

Evolution of Multi-Domain Proteins

22nd June 2004

Author: Sarah Teichmann (MRC Laboratory of Molecular Biology)

Abstract

Two thirds of all prokaryote proteins, and eighty percent of eukaryote proteins are multi-domain proteins. The composition and interaction of the domains within a multi- domain protein determine its function. Using structural assignments to the proteins in completely sequenced genomes, we have insight into the domain architectures of a large fraction of all multi-domain proteins. Thus we can investigate the patterns of pairwise domain combinations, as well as the existence of evolutionary units larger than individual protein domains. Structural assignments provide us with the sequential arrangement of domains along a polypeptide chain. In order to fully understand the structure and function of a multi-domain protein, we also need to know the geometry of the domains relative to each other in three dimensions. By studying multi-domain proteins of known three- dimensional structure, we can gain insight into the conservation of domain geometry, and the prediction of the structures of domain assemblies.