Isogai Yasuhiro, Ota Motonori, Ishii Anna, Ishida Manabu, Nishikawa Ken
The Institute of Physical and Chemical Research (RIKEN), 2-1 Hirosawa, Wako, Saitama 351-0198, Japan.
Protein Eng. 2002 Jul;15(7):555-60. doi: 10.1093/protein/15.7.555.
Structural uniqueness is characteristic of native proteins and is essential to express their biological functions. The major factors that bring about the uniqueness are specific interactions between hydrophobic residues and their unique packing in the protein core. To find the origin of the uniqueness in their amino acid sequences, we analyzed the distribution of the side chain rotational isomers (rotamers) of hydrophobic amino acids in protein tertiary structures and derived deltaS(contact), the conformational-entropy changes of side chains by residue-residue contacts in each secondary structure. The deltaS(contact) values indicate distinct tendencies of the residue pairs to restrict side chain conformation by inter-residue contacts. Of the hydrophobic residues in alpha-helices, aliphatic residues (Leu, Val, Ile) strongly restrict the side chain conformations of each other. In beta-sheets, Met is most strongly restricted by contact with Ile, whereas Leu, Val and Ile are less affected by other residues in contact than those in alpha-helices. In designed and native protein variants, deltaS(contact) was found to correlate with the folding-unfolding cooperativity. Thus, it can be used as a specificity parameter for designing artificial proteins with a unique structure.
结构独特性是天然蛋白质的特征，对于表达其生物学功能至关重要。导致这种独特性的主要因素是疏水残基之间的特定相互作用及其在蛋白质核心中的独特堆积方式。为了探寻其氨基酸序列独特性的起源，我们分析了蛋白质三级结构中疏水氨基酸侧链旋转异构体（旋转异构体）的分布，并得出了ΔS(contact)，即每个二级结构中残基间接触导致的侧链构象熵变化。ΔS(contact)值表明了残基对通过残基间接触限制侧链构象的明显趋势。在α-螺旋中的疏水残基中，脂肪族残基（亮氨酸、缬氨酸、异亮氨酸）强烈限制彼此的侧链构象。在β-折叠中，甲硫氨酸与异亮氨酸接触时受到的限制最强，而亮氨酸、缬氨酸和异亮氨酸与α-螺旋中的残基相比，受其他接触残基的影响较小。在设计的和天然的蛋白质变体中，发现ΔS(contact)与折叠-去折叠协同性相关。因此，它可以用作设计具有独特结构的人工蛋白质的特异性参数。
