Alanine is helix-stabilizing in both template-nucleated and standard peptide helices
Alanine is helix-stabilizing in both template-nucleated and standard peptide helices
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DOI：
10.1073/pnas.96.7.3682
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发表时间：
1999-03-30
影响因子：
11.1
通讯作者：
Baldwin, RL
中科院分区：
文献类型：
--
作者：
Rohl, CA;Fiori, W;Baldwin, RL
具有确定序列和长度的基于丙氨酸的肽显示出可测量的螺旋含量，使它们能够用作分析螺旋形成机制和研究侧链相互作用对蛋白质稳定性的贡献的模型系统。对具有不同氨基酸含量的许多肽序列的广泛表征表明，基于丙氨酸的肽的有利螺旋性可归因于丙氨酸的大螺旋稳定性倾向。基于对富含丙氨酸的序列N末端的分析Kemp 和同事将其与合成螺旋诱导模板连接起来 [Kemp, D, S,, Boyd, J, G, & Muendel, C, C, (1991) Nature (London) 352, 451-354； Kemp, D, S,、Oslick, S, L 和 Alien, T, J, (1996) J, Am。化学。秒。 [118, 4249-4255] 认为丙氨酸是螺旋无关的，然而，基于丙氨酸的肽的有利螺旋含量必须有其他一些解释。在这里，我们表明模板有核序列的螺旋含量受到模板螺旋连接特性的强烈影响。单独处理模板-肽连接处残基的螺旋倾向的模型使基于丙氨酸的肽和模板有核螺旋的结果一致。由此产生的模型为两个系统之间的差异提供了物理上合理的解决方案，并允许通过使用一组螺旋倾向来预测模板有核和标准肽螺旋的螺旋含量。标准肽和模板-肽缀合物中的螺旋形成可归因于丙氨酸的大的内在螺旋形成倾向。
Alanine-based peptides of defined sequence and length show measurable helix contents, allowing them to be used as a model system both for analyzing the mechanism of helix formation and for investigating the contributions of side-chain interactions to protein stability, Extensive characterization of many peptide sequences with varying amino acid contents indicates that the favorable helicity of alanine-based peptides can be attributed to the large helix-stabilizing propensity of alanine, Based on their analysis of alanine-rich sequences N-terminally linked to a synthetic helix-inducing template, Kemp and coworkers [Kemp, D, S,, Boyd, J, G, & Muendel, C, C, (1991) Nature (London) 352, 451-354; Kemp, D, S,, Oslick, S, L, & Alien, T, J, (1996) J, Am. Chem. Sec. 118, 4249-4255] argue that alanine is helix-indifferent, however, and that the favorable helix contents of alanine-based peptides must have some other explanation. Here, we show that the helix contents of template-nucleated sequences are influenced strongly by properties of the template-helix junction. A model in which the helix propensities of residues at the template-peptide junction are treated separately brings the results from alanine-based peptides and template-nucleated helices into agreement. The resulting model provides a physically plausible resolution of the discrepancies between the two systems and allows the helix contents of both template-nucleated and standard peptide helices to be predicted by using a single set of helix propensities. Helix formation in both standard peptides and template-peptide conjugates can be attributed to the large intrinsic helix-forming tendency of alanine.