生物谷报道：内化素B（Internalin B）的富亮氨酸重复域是由7个富亮氨酸的重复单元串联组成的。其中每个单元包含一个短β链，通过一个转折连接到310螺旋以及一个N末端α-螺旋的顶部模体（motif）上。那么上述蛋白质的折叠途径是单一的、不连续的，还是通过多种形式并行进行的？
为了阐明这个问题，Courtemanche和Barrick研究了不稳定替代每个重复单元的保守残基的整体效应，并且绘制了过渡态的整体结构图。结果表明，尽管在重复单元里存在结构性过剩现象，但是过渡态的折叠过程是通过一个N末端进行总体控制，结构形成的程度偏向重复单元1和2，以及包括局部与重复单元之间的互动。
这项研究结果表明，在过渡态时，N末端顶部模体通过在一个快速成长的核子上连续地重复折叠来极化折叠路径，同时该研究也强调了序列特异性相互作用在途径选择上的重要性。（生物谷www.bioon.com）
生物谷推荐原始出处：
Structure，Vol 16, 705-714, 07 May 2008，Naomi Courtemanche and Doug Barrick
The Leucine-Rich Repeat Domain of Internalin B Folds along a Polarized N-Terminal Pathway
Naomi Courtemanche1 and Doug Barrick1,
1 T.C. Jenkins Department of Biophysics, The Johns Hopkins University, 3400 North Charles Street, Baltimore, MD 21218, USA
Summary
The leucine-rich repeat domain of Internalin B is composed of seven tandem leucine-rich repeats, which each contain a short β strand connected to a 310 helix by a short turn, and an N-terminal α-helical capping motif. To determine whether folding proceeds along a single, discrete pathway or multiple, parallel pathways, and to map the structure of the transition state ensemble, we examined the effects of destabilizing substitutions of conserved residues in each repeat. We find that, despite the structural redundancy among the repeats, folding proceeds through an N-terminal transition state ensemble in which the extent of structure formation is biased toward repeats one and two and includes both local and interrepeat interactions. Our results suggest that the N-terminal capping motif serves to polarize the folding pathway by acting as a fast-growing nucleus onto which consecutive repeats fold in the transition state ensemble, and highlight the importance of sequence-specific interactions in pathway selection.
