Paliakasis C D, Kokkinidis M
University of Crete, Department of Biology, Iraklion, Greece.
Protein Eng. 1992 Dec;5(8):739-48. doi: 10.1093/protein/5.8.739.
The sequences of four-alpha-helical bundle proteins are characterized by a pattern of hydrophilic and hydrophobic amino acids which is repeated every seven residues. At each position of the heptad repeat there are specific constraints on the amino acid properties which result from the topology of the tertiary motif. These constraints give rise to patterns of amino acid distribution which are distinct from those of other proteins. The distributions in each of the heptad positions have been determined by a statistical analysis of structural and sequence data derived from seven families of aligned protein sequences. The constitution of each position is dominated by a very small number of different amino acids, with the core positions consisting overwhelmingly of Leu and Ala. The positional preferences of the individual amino acids can be generally interpreted in terms of residue properties and topological constraints. The potential for four-alpha-helix bundle folding is reflected primarily in the pattern of residue occurrence in the heptad and not in the overall amino acid composition of the protein. Possible applications of this analysis in structure predictions, sequence alignments and in the rational design and engineering of four-alpha-helical bundle proteins are discussed.
四螺旋束蛋白的序列具有亲水性和疏水性氨基酸的模式，该模式每七个残基重复一次。在七肽重复序列的每个位置，由于三级基序的拓扑结构，对氨基酸特性存在特定限制。这些限制导致了与其他蛋白质不同的氨基酸分布模式。通过对来自七个比对蛋白质序列家族的结构和序列数据进行统计分析，确定了七肽每个位置的分布情况。每个位置的组成主要由极少数不同的氨基酸主导，核心位置绝大多数由亮氨酸和丙氨酸组成。单个氨基酸的位置偏好通常可以根据残基特性和拓扑限制来解释。四螺旋束折叠的可能性主要反映在七肽中残基出现的模式上，而不是蛋白质的整体氨基酸组成上。讨论了该分析在结构预测、序列比对以及四螺旋束蛋白的合理设计和工程中的可能应用。
