Conversion of monomeric protein L to an obligate dimer by computational protein design.

Kuhlman, B; O'Neill, J W; Kim, D E; Zhang, K Y; Baker, D · Proc Natl Acad Sci U S A · 2001

basic_science · Level V

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Abstract

Protein L consists of a single alpha-helix packed on a four-stranded beta-sheet formed by two symmetrically opposed beta-hairpins. We use a computer-based protein design procedure to stabilize a domain-swapped dimer of protein L in which the second beta-turn straightens and the C-terminal strand inserts into the beta-sheet of the partner. The designed obligate dimer contains three mutations (A52V, N53P, and G55A) and has a dissociation constant of approximately 700 pM, which is comparable to the dissociation constant of many naturally occurring protein dimers. The structure of the dimer has been determined by x-ray crystallography and is close to the in silico model.

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