THE STRUCTURAL BASIS OF SEQUENCE-INDEPENDENT PEPTIDE BINDING BY OPPA PROTEIN

Specific protein-ligand interactions are critical for cellular functio n, and most proteins select their partners with sharp discrimination. However, the oligopeptide-binding protein of Salmonella typhimurium (O ppA) binds peptides of two to five amino acid residues without regard to sequence. The crystal structure of OppA reveals a three-domain orga nization, unlike other periplasmic binding proteins. In OppA-peptide c omplexes, the ligands are completely enclosed in the protein interior, a mode of binding that normally imposes tight specificity. The protei n fulfills the hydrogen bonding and electrostatic potential of the lig and main chain and accommodates the peptide side chains in voluminous hydrated cavities.