Hot-spot residues at the E9/Im9 interface help binding via different mechanisms.
Protein-protein association involves many interface interactions, but they do not contribute equally. Ala scanning experiments reveal that only a few mutations significantly lower binding affinity. These key residues, which appear to drive protein-protein association, are called hot-spot residues. Molecular dynamics simulations of the Colicin E9/Im9 complex show Im9 Glu41 and Im9 Ser50, both hot-spots, bind via different mechanisms. The results suggest that Im9 Ser50 restricts Glu41 in a conformation auspicious for salt-bridge formation across the interface. This type of model may be helpful in engineering hot-spot clusters at protein-protein interfaces and, consequently, the design of specificity.
Department of Chemistry and Biochemistry, University of California at San Diego, LA Jolla, CA 92093-0365, USA. swong@mccammon.ucsd.edu
Sergio E
SE
Wong
Riccardo
R
Baron
J Andrew
JA
McCammon
D000818:Animals; D003087:Colicins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D003851:Deoxyribonucleases / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D006801:Humans; D008958:Models, Molecular; D009154:Mutation; D011485:Protein Binding / Q000235:genetics; D020836:Protein Structure, Quaternary / Q000235:genetics
D003087:Colicins; C488859:immE9 protein, E coli; D003851:Deoxyribonucleases