Tsai Hui-Hsu Gavin, Gunasekaran Kannan, Nussinov Ruth
Department of Chemistry, National Central University, Chung-Li 32001, Taiwan.
Structure. 2006 Jun;14(6):1059-72. doi: 10.1016/j.str.2006.03.015.
Increasing evidence suggests that amyloids and parallel beta helices may share similar motifs. A systemic analysis of beta helices is performed to examine their sequence and structural characteristics. Ile prefers to occur in beta strands. In contrast, Pro is disfavored, compatible with the underlying assumption in Pro-scanning mutagenesis. Cys, Asn, and Phe form significant homostacking (identical amino acid interactions). Asn is highly conserved in the high-energy, left-handed alpha-helical conformation, where it frequently forms amide stacking. Based on the observed prominent stacking of chemically similar residues in parallel beta helices, we propose that within the "cross-beta" framework, amyloids with longer peptide chains may have common structural features of in-register, parallel alignment, with the side chains forming identical amino acid ladders. The requirement of ladder formation limits the combinations of side chain interactions. Such a limit combined with environmental conditions (e.g., pH, concentration) could be a major reason for the ability of most polypeptides to form amyloids.
越来越多的证据表明，淀粉样蛋白和平行β螺旋可能具有相似的基序。对β螺旋进行了系统分析，以研究其序列和结构特征。异亮氨酸倾向于出现在β链中。相比之下，脯氨酸则不受青睐，这与脯氨酸扫描诱变中的潜在假设一致。半胱氨酸、天冬酰胺和苯丙氨酸形成显著的同型堆积（相同氨基酸相互作用）。天冬酰胺在高能左旋α螺旋构象中高度保守，在该构象中它经常形成酰胺堆积。基于在平行β螺旋中观察到的化学相似残基的显著堆积，我们提出，在“交叉β”框架内，具有较长肽链的淀粉样蛋白可能具有共线、平行排列的共同结构特征，其侧链形成相同的氨基酸阶梯。阶梯形成的要求限制了侧链相互作用的组合。这种限制与环境条件（如pH值、浓度）相结合，可能是大多数多肽形成淀粉样蛋白能力的主要原因。
