HIV-1 gp41 tertiary structure studied by EPR spectroscopy.
HIV-1 gp41 tertiary structure studied by EPR spectroscopy.
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通过 EPR 光谱研究 HIV-1 gp41 三级结构。
DOI：
10.1021/bi961743t
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发表时间：
1996
期刊：
影响因子：
--
通讯作者：
Shin,YK
中科院分区：
文献类型：
--
作者：
Rabenstein,MD;Shin,YK
HIV gp41 是一种跨膜糖蛋白，负责病毒和细胞膜的融合，从而使病毒能够进入。使用源自 gp41 胞外域的两种合成肽研究了 gp41 的结构：来自“七肽重复”区域 (hr.wt) 的 38 个残基肽，以及来自更靠近 C 末端的区域的 34 个残基肽 (bt.wt)。发现这些肽形成具有大约 80% α 螺旋度的异二聚体三聚体。为了研究它们的排列，使用最近开发的电子顺磁共振方法测量了连接到 Cys 取代肽上的 Cys 残基的自旋标记之间的距离 [Rabenstein, M. D., & Shin, Y.-K. (1995)国家科学院院刊。阿卡德。科学。美国 92, 8239−8243]。发现异源三聚肽是反平行的，与 gp41 蛋白水解切割肽片段的研究一致 [Lu, M., Blacklow, S. C., & Kim, P. S. (1995)Nat.结构。生物。 2,1075−1082]。此外，hr.wt的C端19个残基不与bt.wt并列，并且bt.wt的15个残基延伸超出hr.wt的末端。与这种比对一致的是通过自旋标记迁移率探测到的这些肽的特定位点之间的三级相互作用。此外，还研究了第二对肽。从模型来看，这些预计将完全重叠。单独使用时，两者都不是螺旋形，但混合后，它们的 83% 是螺旋形的。基于肽的比对，构建了gp41的融合前形式的模型，该模型与流感血凝素的结构显着不同。
HIV gp41 is the transmembrane glycoprotein responsible for fusion of viral and cellular membranes, enabling viral entry. The structure of gp41 was studied using two synthetic peptides derived from the ectodomain of gp41: a 38-residue peptide from the “heptad repeat” region (hr.wt), and a 34-residue peptide from a region closer to the C-terminus (bt.wt). These peptides were found to form a trimer of heterodimers with approximately 80% α-helicity. To study their alignment, distances between spin-labels attached to Cys residues on Cys-substituted peptides were measured using a recently-developed electron paramagnetic resonance method [Rabenstein, M. D., & Shin, Y.-K. (1995)Proc.Natl. Acad. Sci. U.S.A. 92, 8239−8243]. The heterotrimeric peptides were found to be antiparallel, consistent with a study on proteolytically cleaved peptide fragments of gp41 [Lu, M., Blacklow, S. C., & Kim, P. S. (1995)Nat. Struct. Biol. 2,1075−1082]. Furthermore, the C-terminal 19 residues of hr.wt are not apposed to bt.wt, and 15 residues of bt.wt extend beyond the end of hr.wt. Consistent with this alignment are tertiary interactions between specific sites of these peptides probed by spin-label mobility. Additionally, a second pair of peptides was studied. From the model, these are expected to align with complete overlap. Alone, neither was helical, but when mixed, they were 83% helical. Based on the alignment of the peptides, a model of the prefusogenic form of gp41 was constructed which is significantly different from the structure of influenza hemagglutinin.