Structure-Function Relationship of Bacterial SH3 Domains

Abstract

The Src Homology 3 domain (SH3 domain) is a protein domain that has been identified in the diverse signaling and cytoskeletal proteins of eukaryotes. A typical SH3 domain is composed of a β-structure consisting of five β-strands connected by three loops, called the RT loop, n-Src loop, and distal loop, and a short 310 helix. A Pro-rich peptide ligand binds to a groove flanked by the RT loop and a short 310 helix. SH3-like domains in prokaryotes have been predicted to act as the targeting domains involved in bacterial cell wall recognition and binding, and the bacterial SH3 domain has been identified in various bacteria with some variations. The most prominent difference in structure between the eukaryote and bacterial SH3 domains is in the RT loop. The bacterial SH3 domains have long insertions of amino acids in the RT loop, by which the corresponding region to the peptide ligand-binding site of the eukaryote SH3 domain is disrupted. This finding indicated that bacterial SH3 domains perform their functions in different manners from eukaryote SH3 domains. We herein provided an overview of the structure-function relationship of bacterial SH3 domains, on the domains targeting the bacterial cell wall, and the domains involved in metal-binding based on their X-ray structures.