· H. Remaut and G. Waksman
Protein-protein interaction through beta-strand addition
TIBS. 34:436-444 (2006)
Protein-protein interactions play
essential roles at almost any level of organization and communication in living
cells. During complex formation, proteins can interact by means of 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 PDB identifies beta-strand additions in many important
metabolic pathways. Targeting these interactions may thus provide novel routes
in rational drug design.