Distinct Peptide Binding Specificities of Src Homology 3 (SH3) Protein Domains Can Be Determined by Modulation of Local Energetics across the Binding Interface

Abstract

Background: Two SH3 domains investigated are cross-reactive in peptide binding, yet also display highly divergent specificities. Results: These domains interact with peptides in a structurally similar manner, but differ in interaction strength formed with different regions of peptides. Conclusion: Distinct specificities of these domains arise from differences in local binding energetics. Significance: A new mechanism for generating binding specificity is demonstrated.

Yeast Adaptor Protein, Nbp2p, Is Conserved Regulator of Fungal Ptc1p Phosphatases and Is Involved in Multiple Signaling Pathways

“…5A). These sites displayed strong conservation at several positions outside of the RXXPXXP canonical Class I SH3 domain binding site that we have shown to be important for Nbp2p binding (30), implying that the Nbp2p SH3 domain binds to Bck1p in all of these species.…”

Protein-Peptide Interactions Revolutionize Drug Development

“…It has become apparent that a significant number of protein interactions are commonly formed between conserved protein recognition domains and short linear peptide motifs, often less than 10 amino acids in length [14][15][16][17]. Members of a given protein domain family usually recognize a consensus motif but they may recognize different variations of this motif and they may possess unique binding specificities [17][18][19][20][21][22][23][24].…”

“…Members of a given protein domain family usually recognize a consensus motif but they may recognize different variations of this motif and they may possess unique binding specificities [17][18][19][20][21][22][23][24].…”

“…-amyloid fibrillogenesis involves the conversion of -helix/random coil to -sheet motifs and proceeds via oligomeric and protofibrillar intermediates therefore it can be inhibited by destabilizing the -sheet-rich -amyloid intermediates, using -sheet breaker peptides [146][147][148][149]. One example of a -sheet breaker peptide, which comprises a short fragment of -amyloid peptide (KLVFF; residues [16][17][18][19][20], can bind full-length -amyloid peptide and prevent its assembly into amyloid fibrils [150]. The peptide LPFFD derived from another fragment of the -amyloid peptide (LVFFA; residues 17-21) is another -sheet breaker that abolishes fibril formation [146,147] .…”

A time resolved interaction analysis of Bem1 reconstructs the flow of Cdc42 during polar growth

“…However, the removal of SH3 a hardly affects secretory vesicle fusion or other aspects of polarized growth (France et al, 2006). SH3 b interacts with well-characterized PxxP motives in the PAKs Cla4 and Ste20, and the polarity proteins Boi1 and Boi2 (Winters and Pryciak, 2005;Bender et al, 1996;Bose et al, 2001;Gorelik and Davidson, 2012). SH3 b harbors a C-terminal extension (CI) that binds Cdc42 GTP without impairing the interaction with its PxxP ligands (Takaku et al, 2010;Yamaguchi et al, 2007).…”