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Hot-spot residues at the E9/Im9 interface help binding via different mechanisms.

ABSTRACT: 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.

SUBMITTER: Wong SE

PROVIDER: S-EPMC2575057 | biostudies-literature | 2008 Nov

REPOSITORIES: biostudies-literature

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Hot-spot residues at the E9/Im9 interface help binding via different mechanisms.

Wong Sergio E SE Baron Riccardo R McCammon J Andrew JA

Biopolymers 20081101 11

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 conform ...[more]

PMID: 18546205

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