Bilayer surface association of the pHLIP peptide promotes extensive backbone desolvation and helically-constrained structures
Bilayer surface association of the pHLIP peptide promotes extensive backbone desolvation and helically-constrained structures
复制标题
DOI：
10.1016/j.bpc.2013.12.004
复制
发表时间：
2014-03-01
影响因子：
3.8
通讯作者：
Cooley, Jason W.
中科院分区：
文献类型：
--
作者：
Brown, Mia C.;Yakubu, Rauta A.;Cooley, Jason W.
尽管膜蛋白存在于生物学的许多方面，但对膜蛋白的研究落后于可溶性蛋白。改善膜蛋白的结构分析是必不可少的。深紫外共振拉曼（DUVRR）光谱是这一领域的新兴技术，并已证明敏感性的微妙的结构转变和蛋白质环境的变化。pH低插入肽（pHLIP）具有三种不同的结构状态：在水性环境中无序、部分折叠并与脂质膜缔合以及作为跨膜螺旋插入脂质双层中。虽然可溶性和膜插入的形式是很好的特点，部分折叠的膜相关的状态尚未明确描述。已知对蛋白质环境敏感的酰胺I模式在膜相关和膜插入pHLIP的光谱中是相同的，表明骨架脱水的水平相当。酰胺S模式，敏感的螺旋结构，表明较少的螺旋字符在膜相关的形式相比，膜插入状态，与以前的研究结果一致。然而，结构敏感的酰胺III区是非常相似的膜相关和膜插入的pHLIP，这表明膜相关的形式有大量的有序结构。在此之前，膜相关状态被认为主要包含无序结构并主要存在于水性环境中，我们已经证明它包含大量有序结构并位于脂质膜的更深处。(C)2013爱思唯尔有限公司版权所有。
Despite their presence in many aspects of biology, the study of membrane proteins lags behind that of their soluble counterparts. Improving structural analysis of membrane proteins is essential. Deep-UV resonance Raman (DUVRR) spectroscopy is an emerging technique in this area and has demonstrated sensitivity to subtle structural transitions and changes in protein environment. The pH low insertion peptide (pHLIP) has three distinct structural states: disordered in an aqueous environment, partially folded and associated with a lipid membrane, and inserted into a lipid bilayer as a transmembrane helix. While the soluble and membrane-inserted forms are well characterized, the partially folded membrane-associated state has not yet been clearly described. The amide I mode, known to be sensitive to protein environment, is the same in spectra of membrane-associated and membrane-inserted pHLIP, indicating comparable levels of backbone dehydration. The amide S mode, sensitive to helical structure, indicates less helical character in the membrane-associated form compared to the membrane-inserted state, consistent with previous findings. However, the structurally sensitive amide III region is very similar in both membrane-associated and membrane-inserted pHLIP, suggesting that the membrane-associated form has a large amount of ordered structure. Where before the membrane-associated state was thought to contain mostly unordered structure and reside in a predominantly aqueous environment, we have shown that it contains a significant amount of ordered structure and rests deeper within the lipid membrane. (C) 2013 Elsevier B.V. All rights reserved.