5npo

Publication Abstract from PubMed

Proteins have evolved to balance efficient binding of desired partners with rejection of unwanted interactions. To investigate the evolution of protein-protein interactions, we selected a random library of pre-stabilized TEM1 beta-lactamase against wild-type TEM1 using yeast surface display. Three mutations were sufficient to achieve micromolar affinity binding between the two. The X-ray structure emphasized that the main contribution of the selected mutations was to modify the protein fold, specifically removing the N'-terminal helix, which consequently allowed protein coupling via a beta-sheet-mediated interaction resembling amyloid interaction mode. The only selected mutation located at the interaction interface (E58V) is reminiscent of the single mutation commonly causing sickle-cell anemia. Interestingly, the evolved mutations cannot be inserted into the wild-type protein due to reduced thermal stability of the resulting mutant protein. These results reveal a simple mechanism by which undesirable binding is purged by loss of thermal stability.

Promiscuous Protein Binding as a Function of Protein Stability.,Cohen-Khait R, Dym O, Hamer-Rogotner S, Schreiber G Structure. 2017 Dec 5;25(12):1867-1874.e3. doi: 10.1016/j.str.2017.11.002. PMID:29211984^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.