Complementation of buried lysine and surface polar residues in a designed heterodimeric coiled coil.
Complementation of buried lysine and surface polar residues in a designed heterodimeric coiled coil.
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设计的异二聚体卷曲线圈中埋藏赖氨酸和表面极性残基的互补。
DOI：
10.1021/bi025559l
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发表时间：
2002
期刊：
影响因子：
2.9
通讯作者：
Lumb,KevinJ
中科院分区：
文献类型：
--
作者：
Campbell,KathleenM;Lumb,KevinJ
卷曲线圈是蛋白质设计的一个有吸引力的目标。卷曲螺旋的螺旋特征在于表示残基的七元重复。位于形成螺旋间界面的位置a和d的残基通常是疏水性的。赋予双链卷曲线圈结构独特性的既定策略是在位置a使用埋藏的极性Asn残基，这以牺牲稳定性为代价赋予二聚化和构象特异性。在这里，我们表明，涉及埋藏位置的 aLys 残基的极性相互作用只能与表面“org”Glu 残基有利地相互作用，也赋予设计的异二聚体卷曲线圈结构独特性，具有 S 形热和尿素诱导的展开转变、缓慢的氢交换和缺乏 ANS 结合的天然特性。然而，位置 aLys 残基并不赋予对螺旋方向的单一偏好，这可能反映了位置 aLys 的能力，分别与平行和反平行方向的 g'ore' Glu 残基有利的相互作用。 Lys-Glu 极性相互作用比 Asn-Asna→a’ 相互作用的不稳定程度更小，这可能反映了与完全埋藏的极性位置 agroup 相关的更高的去溶剂化惩罚。我们的结果扩展了双链卷曲螺旋设计的方法范围，并说明了在蛋白质折叠和设计中与蛋白质埋藏和表面位置相关的互补极性基团的作用。
The coiled coil is an attractive target for protein design. The helices of coiled coils are characterized by a heptad repeat of residues denotedatog. Residues at positionsaanddform the interhelical interface and are usually hydrophobic. An established strategy to confer structural uniqueness to two-stranded coiled coils is the use of buried polar Asn residues at positiona, which imparts dimerization and conformational specificity at the expense of stability. Here we show that polar interactions involving buried position-aLys residues that can interact favorably only with surfacee‘ org‘ Glu residues also impart structural uniqueness to a designed heterodimeric coiled coil with the nativelike properties of sigmoidal thermal and urea-induced unfolding transitions, slow hydrogen exchange and lack of ANS binding. The position-aLys residues do not, however, confer a single preference for helix orientation, likely reflecting the ability of Lys at positionato from favorable interactions withg‘ ore‘ Glu residues in the parallel and antiparallel orientations, respectively. The Lys-Glu polar interaction is less destabilizing than the Asn-Asna→a‘ interaction, presumably reflecting a higher desolvation penalty associated with the completely buried polar position-agroups. Our results extend the range of approaches for two-stranded coiled-coil design and illustrate the role of complementing polar groups associated with buried and surface positions of proteins in protein folding and design.
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影响因子：
5.6
作者：
Walshaw, J;Woolfson, DN
通讯作者：
Woolfson, DN
关于球状蛋白中可电离基团的环境。
影响因子：
5.6
作者：
Rashin,AA;Honig,B
通讯作者：
Honig,B
从头设计的蛋白质模仿天然蛋白质的天然状态
DOI：
--
发表时间：
1995
期刊：
影响因子：
--
作者：
D. Raleigh;S. Betz;W. DeGrado
通讯作者：
W. DeGrado
影响因子：
5.6
作者：
Eckert, DM;Malashkevich, VN;Kim, PS
通讯作者：
Kim, PS