Protein-protein interaction through beta-strand addition.
Protein-protein interactions have essential roles at almost every level of organization and communication in living cells. During complex formation, proteins can interact via covalent, surface-surface or peptide-surface contacts. Many protein complexes are now known to involve the binding of linear motifs in one of the binding partners. An emerging mechanism of such non-covalent peptide-surface interaction involves the donation or addition of a beta strand in the ligand to a beta sheet or a beta strand in the receptor. Such 'beta-strand addition' contacts can dictate or modulate binding specificity and affinity, or can be used in more promiscuous protein-protein contacts. Three main classes of beta-strand addition can be distinguished: beta-sheet augmentation; beta-strand insertion and fold complementation; and beta-strand zippering. A survey of protein-protein complexes in the protein data bank identifies beta-strand additions in many important metabolic pathways. Targeting these interactions might, thus, provide novel routes for rational drug design.
Remaut
Han
H
Institute of Structural Molecular Biology, School of Crystallography, Birkbeck College, University College London, London, WC1E 7HX, UK.
Waksman
Gabriel
G
D000818:Animals; D001665:Binding Sites; D006801:Humans; D008958:Models, Molecular; D011485:Protein Binding; D017510:Protein Folding; D017433:Protein Structure, Secondary; D011506:Proteins / Q000737:chemistry* / Q000378:metabolism
D011506:Proteins