Laboratory of Chemical Physics and ‡Laboratory of Molecular Biology, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health , Bethesda, Maryland 20892, United States.
J Am Chem Soc. 2018 Jan 10;140(1):34-37. doi: 10.1021/jacs.7b10245. Epub 2017 Dec 27.
Cryo-electron microscopy and X-ray crystallography have shown that the pre- and postfusion states of the HIV-1 gp41 viral coat protein, although very different from one another, each adopt C symmetric structures. A stable homotrimeric structure for the transmembrane domain (TM) also was modeled and supported by experimental data. For a C symmetric structure, alignment in an anisotropic medium must be axially symmetric, with the unique axis of the alignment tensor coinciding with the C axis. However, NMR residual dipolar couplings (RDCs) measured under three different alignment conditions were found to be incompatible with C symmetry. Subsequent measurements by paramagnetic relaxation enhancement, analytical ultracentrifugation, and DEER EPR, indicate that the transmembrane domain is monomeric. N NMR relaxation data and RDCs show that TM is highly ordered and uninterrupted for a total length of 32 residues, extending well into the membrane proximal external region.
冷冻电子显微镜和 X 射线晶体学已经表明，HIV-1 gp41 病毒外壳蛋白的融合前和融合后状态虽然彼此非常不同，但都采用 C 对称结构。还对跨膜结构域 (TM) 的稳定同源三聚体结构进行了建模，并得到了实验数据的支持。对于 C 对称结构，各向异性介质中的对齐必须是轴对称的，并且对齐张量的唯一轴与 C 轴重合。然而，在三种不同的对准条件下测量的 NMR 残余偶极耦合 (RDC) 与 C 对称不兼容。随后通过顺磁弛豫增强、分析超速离心和 DEER EPR 的测量表明，跨膜结构域是单体的。NMR 弛豫数据和 RDC 表明 TM 高度有序且完整，总长度为 32 个残基，延伸到膜近端外部区域。
