生物谷報道：內(nèi)化素B（Internalin B）的富亮氨酸重復(fù)域是由7個富亮氨酸的重復(fù)單元串聯(lián)組成的,。其中每個單元包含一個短β鏈，通過一個轉(zhuǎn)折連接到310螺旋以及一個N末端α-螺旋的頂部模體（motif）上,。那么上述蛋白質(zhì)的折疊途徑是單一的,、不連續(xù)的，還是通過多種形式并行進(jìn)行的,？
為了闡明這個問題,，Courtemanche和Barrick研究了不穩(wěn)定替代每個重復(fù)單元的保守殘基的整體效應(yīng)，并且繪制了過渡態(tài)的整體結(jié)構(gòu)圖,。結(jié)果表明,，盡管在重復(fù)單元里存在結(jié)構(gòu)性過剩現(xiàn)象,，但是過渡態(tài)的折疊過程是通過一個N末端進(jìn)行總體控制,，結(jié)構(gòu)形成的程度偏向重復(fù)單元1和2，以及包括局部與重復(fù)單元之間的互動,。
這項研究結(jié)果表明,，在過渡態(tài)時，N末端頂部模體通過在一個快速成長的核子上連續(xù)地重復(fù)折疊來極化折疊路徑,，同時該研究也強(qiáng)調(diào)了序列特異性相互作用在途徑選擇上的重要性,。（生物谷www.bioon.com）
生物谷推薦原始出處：
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.
