Nautiyal S, Woolfson D N, King D S, Alber T
Department of Molecular and Cell Biology, University of California, Berkeley 94720-3206, USA.
Biochemistry. 1995 Sep 19;34(37):11645-51. doi: 10.1021/bi00037a001.
Principles that guide folding of coiled coils were tested by designing three peptides that preferentially associate with each other to form a heterotrimeric coiled coil. The core positions of the designed helices contained residues that promote formation of trimeric coiled coils. Ionic interactions were employed to mediate heterospecificity, and negative design was used to favor formation of the heterotrimer over alternative arrangements. A program was written to select sequences that maximized the number of attractive interhelical interactions in a parallel heterotrimer and the number of repulsive electrostatic interactions in alternative species. Solution studies indicate that an equimolar mixture of the three peptides forms a helical trimer with high specificity and stability. These results validate the principles used to guide the design and suggest that the heterotrimer may serve as a useful, autonomous trimerization domain.
通过设计三种优先相互结合形成异源三聚体卷曲螺旋的肽，对指导卷曲螺旋折叠的原则进行了测试。设计的螺旋的核心位置包含促进三聚体卷曲螺旋形成的残基。利用离子相互作用介导异特异性，并采用负向设计来促进异源三聚体的形成而非其他排列方式。编写了一个程序来选择能使平行异源三聚体中吸引性螺旋间相互作用的数量以及其他物种中排斥性静电相互作用的数量最大化的序列。溶液研究表明，三种肽的等摩尔混合物形成了具有高特异性和稳定性的螺旋三聚体。这些结果验证了用于指导设计的原则，并表明异源三聚体可能作为一个有用的自主三聚化结构域。
