Hot spots—A review of the protein–protein interface determinant amino‐acid residues

Abstract

Proteins tendency to bind to one another in a highly specific manner forming stable complexes is fundamental to all biological processes. A better understanding of complex formation has many practical applications, which include the rational design of new therapeutic agents, and the analysis of metabolic and signal transduction networks. Alanine-scanning mutagenesis made possible the detection of the functional epitopes, and demonstrated that most of the protein-protein binding energy is related only to a group of few amino acids at intermolecular protein interfaces: the hot spots. The scope of this review is to summarize all the available information regarding hot spots for a better atomic understanding of their structure and function. The ultimate objective is to improve the rational design of complexes of high affinity and specificity as well as that of small molecules, which can mimic the functional epitopes of the proteic complexes.

A Dominant Negative Heterozygous G87R Mutation in the Zinc Transporter, ZnT-2 (SLC30A2), Results in Transient Neonatal Zinc Deficiency

“…4A) in which glycine (Gly-135), arginine (Arg-138), and glutamate (E140) are highly conserved. We, therefore, theorized that this motif may be important for protein-protein interactions due to the presence of aromatic and charged side chains (46). To examine the possible role of this conserved motif in ZnT-2 homodimerization, we substituted the most conserved core residues in this motif i.e.…”

“…To examine the possible role of this conserved motif in ZnT-2 homodimerization, we substituted the most conserved core residues in this motif i.e. Phe-134, Gly-135, Arg-138, and Glu-140 to alanine using site-directed mutagenesis as previously reported in studies aimed at identification of residues necessary for dimerization (46). All four mutations (i.e.…”

Structure of the protein core of the glypican Dally-like and localization of a region important for hedgehog signaling

“…Curiously, the identified surface is composed largely of hydrophilic residues, which is unusual for protein-protein interfaces (41). This surface also occurs on the opposite surface of Dlp relative to the disordered Dlp-specific insertion that follows the furin-like processing site, suggesting that interactions mediated by this region are likely independent of furin-like processing and this insertion.…”

Involvement of the N-terminal B-box Domain of Arabidopsis BBX32 Protein in Interaction with Soybean BBX62 Protein

“…Complex-Identification of the protein-protein binding interface and detection of specific amino acid residues that can contribute to the specificity and affinity of protein interactions are essential for better understanding complex formation and protein function (38). In an effort to identify the interface of AtBBX32-GmBBX62 interaction, we constructed structural models of the AtBBX32-GmBBX62 complex.…”