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

TitleConversion of monomeric protein L to an obligate dimer by computational protein design
Publication TypeJournal Article
Year of Publication2001
AuthorsKuhlman, B., O'Neill J. W., Kim D. E., Zhang K. Y., & Baker D.
JournalProceedings of the National Academy of Sciences of the United States of America
Volume98
Issue19
Pagination10687-91
Date Published2001 Sep 11
ISSN0027-8424
KeywordsBacterial Proteins, Dimerization, DNA-Binding Proteins, Guanidine, Models, Molecular, Mutagenesis, Primary Publication, Protein Denaturation, Protein Structure, Secondary
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.

Alternate JournalProc. Natl. Acad. Sci. U.S.A.
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