2MG2
NMR assignment and structure of a peptide derived from the membrane proximal external region of HIV-1 gp41 in the presence of hexafluoroisopropanol
Summary for 2MG2
| Entry DOI | 10.2210/pdb2mg2/pdb |
| Related | 2MG1 2MG3 |
| NMR Information | BMRB: 19582 |
| Descriptor | Transmembrane protein gp41 (1 entity in total) |
| Functional Keywords | hiv-1 gp41 protein, neutralizing epitope, peptide vaccine, mper, viral protein |
| Biological source | Human immunodeficiency virus 1 (HIV-1) |
| Total number of polymer chains | 1 |
| Total formula weight | 3489.31 |
| Authors | Serrano, S.,Apellaniz, B.,Huarte, N.L.,Nieva, J.L.,Jimenez, M.A. (deposition date: 2013-10-24, release date: 2015-03-25, Last modification date: 2024-05-15) |
| Primary citation | Apellaniz, B.,Rujas, E.,Serrano, S.,Morante, K.,Tsumoto, K.,Caaveiro, J.M.,Jimenez, M.A.,Nieva, J.L. The Atomic Structure of the HIV-1 gp41 Transmembrane Domain and Its Connection to the Immunogenic Membrane-proximal External Region. J.Biol.Chem., 290:12999-13015, 2015 Cited by PubMed Abstract: The membrane-proximal external region (MPER) C-terminal segment and the transmembrane domain (TMD) of gp41 are involved in HIV-1 envelope glycoprotein-mediated fusion and modulation of immune responses during viral infection. However, the atomic structure of this functional region remains unsolved. Here, based on the high resolution NMR data obtained for peptides spanning the C-terminal segment of MPER and the TMD, we report two main findings: (i) the conformational variability of the TMD helix at a membrane-buried position; and (ii) the existence of an uninterrupted α-helix spanning MPER and the N-terminal region of the TMD. Thus, our structural data provide evidence for the bipartite organization of TMD predicted by previous molecular dynamics simulations and functional studies, but they do not support the breaking of the helix at Lys-683, as was suggested by some models to mark the initiation of the TMD anchor. Antibody binding energetics examined with isothermal titration calorimetry and humoral responses elicited in rabbits by peptide-based vaccines further support the relevance of a continuous MPER-TMD helix for immune recognition. We conclude that the transmembrane anchor of HIV-1 envelope is composed of two distinct subdomains: 1) an immunogenic helix at the N terminus also involved in promoting membrane fusion; and 2) an immunosuppressive helix at the C terminus, which might also contribute to the late stages of the fusion process. The unprecedented high resolution structural data reported here may guide future vaccine and inhibitor developments. PubMed: 25787074DOI: 10.1074/jbc.M115.644351 PDB entries with the same primary citation |
| Experimental method | SOLUTION NMR |
Structure validation
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