Conversion of monomeric protein L to an obligate dimer by computational protein design
Conversion of monomeric protein L to an obligate dimer by computational protein design
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DOI：
10.1073/pnas.181354398
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发表时间：
2001-09-11
影响因子：
11.1
通讯作者：
Baker, D
中科院分区：
文献类型：
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作者：
Kuhlman, B;O'Neill, JW;Baker, D
蛋白L由单个α-螺旋组成，该α-螺旋包装在由两个对称相对的β-发夹形成的四链β-折叠上。我们使用基于计算机的蛋白质设计程序来稳定蛋白质L的结构域交换二聚体，其中第二个β转角变直，C末端链插入伴侣的β折叠中。所设计的专性二聚体含有三个突变（A52 V、N53 P和G55 A），并且具有约700 pM的解离常数，这与许多天然存在的蛋白质二聚体的解离常数相当。二聚体的结构已通过X射线晶体学测定，并接近于计算机模型。
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.