A BURIED POLAR INTERACTION IMPARTS STRUCTURAL UNIQUENESS IN A DESIGNED HETERODIMERIC COILED-COIL
A BURIED POLAR INTERACTION IMPARTS STRUCTURAL UNIQUENESS IN A DESIGNED HETERODIMERIC COILED-COIL
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DOI：
10.1021/bi00027a013
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发表时间：
1995-07-11
期刊：
影响因子：
2.9
通讯作者：
KIM, PS
中科院分区：
文献类型：
--
作者：
LUMB, KJ;KIM, PS
埋藏的极性残基是天然蛋白质的共同特征。ACID-p1和BASE-p1是两种设计的肽，其形成具有固定三级结构的平行异二聚体卷曲螺旋[O ′ Shea，E.K.，Lumb，K.J.，和Kim，P.S.（1993）Curr. 3，658-667]。ACID-pl和BASE-pl螺旋之间的界面由疏水性Leu残基组成，除了单个极性残基Asn 14。在GCN 4亮氨酸拉链卷曲螺旋的晶体结构中，类似的Asn与相对螺旋的相应Asn氢键合，从而在螺旋之间的另外的疏水界面中形成掩埋的极性相互作用[O ′ Shea，E. K.，Klemm，J.D.，金，附，和Aler，T.（1991）Science 254，539-544]。通过用Leu取代Bsn 14来去除ACID-pl/BBSE-pl异二聚体中的这种掩埋极性相互作用。Asn 14 --> Leu变体比pi肽显著更稳定，并且优先形成异源四聚体而不是异源二聚体。引人注目的是，异源四聚体不会折叠成独特的结构;特别是，螺旋缺乏独特的方向。因此，Asn 14残基以牺牲稳定性为代价赋予形成双链平行卷曲螺旋的特异性。结果表明，而非特异性的疏水相互作用有助于蛋白质的稳定性，以满足埋在蛋白质内部的一般疏水环境中的极性残基的氢键结合潜力的要求可以赋予特异性（结构独特性）的蛋白质折叠和设计。
Buried polar residues are a common feature of natural proteins. ACID-p1 and BASE-pl are two designed peptides that form a parallel, heterodimeric coiled coil with a fixed tertiary structure [O'Shea, E.K., Lumb, K.J., and Kim, P.S. (1993) Curr. Biol. 3, 658-667]. The interface between the ACID-pl and BASE-pl helices consists of hydrophobic Leu residues, with the exception of a single polar residue, Asn 14. In the crystal structure of the GCN4 leucine zipper coiled coil, an analogous Asn is hydrogen bonded to the corresponding Asn of the opposing helix, thereby forming a buried polar interaction in an otherwise hydrophobic interface between the helices [O'Shea, E. K., Klemm, J. D., Kim, P. S., and Aler, T. (1991) Science 254, 539-544]. This buried polar interaction in the ACID-pl/BBSE-pl heterodimer was removed by substituting Bsn 14 with Leu. The Asn 14 --> Leu variants are significantly more stable than the pi peptides and preferentially form a heterotetramer instead of a heterodimer. Strikingly, the heterotetramer does not fold into a unique structure; in particular, the helices lack a unique orientation. Thus, the Asn 14 residue imparts specificity for formation of a two-stranded, parallel coiled coil at the expense of stability. The results suggest that, whereas nonspecific hydrophobic interactions contribute to protein stability, the requirement to satisfy the hydrogen bonding potential of buried polar residues in the generally hydrophobic environment of the protein interior can impart specificity (structural uniqueness) to protein folding and design.