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

被引：68

作者：

Kuhlman, B

O'Neill, JW

Kim, DE

Zhang, KYJ

Baker, D ^{[1
]}

机构：

[1] Univ Washington, Dept Biochem, Seattle, WA 98195 USA

[2] Univ Washington, Howard Hughes Med Inst, Seattle, WA 98195 USA

[3] Fred Hutchinson Canc Res Ctr, Div Basic Sci, Seattle, WA 98109 USA

来源：

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA | 2001年 / 98卷 / 19期

关键词：

D O I：

10.1073/pnas.181354398

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

Protein L consists of a single a-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 approximate to 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.

引用

页码：10687 / 10691

页数：5

共 27 条

[1] High-resolution structure of an engineered cro monomer shows changes in conformation relative to the native dimer [J].