Preferred side-chain constellations at antiparallel coiled-coil interfaces
Preferred side-chain constellations at antiparallel coiled-coil interfaces
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DOI：
10.1073/pnas.0709068105
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发表时间：
2008-01-15
影响因子：
11.1
通讯作者：
Gellman, Samuel H.
中科院分区：
文献类型：
--
作者：
Hadley, Erik B.;Testa, Oliver D.;Gellman, Samuel H.
将蛋白质序列与结构相关联的可靠预测规则将促进后基因组预测生物学以及肽和蛋白质的工程设计和从头设计。通过实验以及对蛋白质数据库（PDB）的分析相结合，我们已经破译并阐明了一种常见蛋白质折叠和缔合基序——反平行二聚卷曲螺旋的螺旋 - 螺旋界面的新规则。这些界面是由主要为疏水性侧链之间的特定相互作用模式所定义的，这种模式通常被称为“旋钮入孔”（KIH）堆积：一个螺旋上的旋钮插入到由其伙伴上的四个残基形成的孔中。先前的工作集中在KIH基序内的横向相互作用上，例如，在反平行卷曲螺旋中一个螺旋上的a位与另一个螺旋上的d'位之间的相互作用。我们表明，KIH基序内的垂直相互作用，例如a' - a - a'，在能量上也是重要的。实验分析和数据库分析在优选的垂直组合方面是一致的，这些组合可以被合理地解释为会产生我们称之为“星座”的有利侧链相互作用。这里呈现的研究结果凸显了卷曲螺旋相互作用中意想不到的复杂程度，并且我们对一些特定“星座”的分析展示了一种解决这种复杂性的通用的、多管齐下的方法。
Reliable predictive rules that relate protein sequence to structure would facilitate postgenorne predictive biology and the engineering and de novo design of peptides and proteins. Through a combination of experiment and analysis of the protein data bank (PDB), we have deciphered and rationalized new rules for helix-helix interfaces of a common protein-folding and association motif, the antiparallel dimeric coiled coil. These interfaces are defined by a specific pattern of interactions among largely hydrophobic side chains often referred to as knobs-into-holes (KIH) packing: a knob from one helix inserts into a hole formed by four residues on the partner. Previous work has focused on lateral interactions within the KIH motif, for example, between an a position on one helix and a d' position on the other in an antiparallel coiled coil. We show that vertical interactions within the KIH motif, such as a'-a-a', are energetically important as well. The experimental and database analyses concur regarding preferred vertical combinations, which can be rationalized as leading to favorable side-chain interactions that we call constellations. The findings presented here highlight an unanticipated level of complexity in coiled-coil interactions, and our analysis of a few specific constellations illustrates a general, multipronged approach to addressing this complexity.