title: Conversion of monomeric protein L to an obligate dimer by computational protein design.
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.
authors.affiliation: Department of Biochemistry and Howard Hughes Medical Institute, University of Washington, Seattle, WA 98195, USA.
authors.forename: B
authors.initials: B
authors.lastname: Kuhlman
authors.forename: J W
authors.initials: JW
authors.lastname: O'Neill
authors.forename: D E
authors.initials: DE
authors.lastname: Kim
authors.forename: K Y
authors.initials: KY
authors.lastname: Zhang
authors.forename: D
authors.initials: D
authors.lastname: Baker
mesh_terms: D001426:Bacterial Proteins; D004268:DNA-Binding Proteins / Q000737:chemistry* / Q000235:genetics; D019281:Dimerization; D019791:Guanidine; D008958:Models, Molecular; D016296:Mutagenesis; D011489:Protein Denaturation; D017433:Protein Structure, Secondary
chemical_list: D001426:Bacterial Proteins; D004268:DNA-Binding Proteins; C116593:L-protein, Peptococcus magnus; D019791:Guanidine