6E8W
MPER-TM Domain of HIV-1 envelope glycoprotein (Env)
Summary for 6E8W
Entry DOI | 10.2210/pdb6e8w/pdb |
NMR Information | BMRB: 30503 |
Descriptor | Envelope glycoprotein gp160 (1 entity in total) |
Functional Keywords | mper-tmd hiv-1 env gp41, viral protein |
Biological source | Human immunodeficiency virus 1 |
Total number of polymer chains | 3 |
Total formula weight | 18538.12 |
Authors | Fu, Q.,Shaik, M.M.,Cai, Y.,Ghantous, F.,Piai, A.,Peng, H.,Rits-Volloch, S.,Liu, Z.,Harrison, S.C.,Seaman, M.S.,Chen, B.,Chou, J.J. (deposition date: 2018-07-31, release date: 2018-09-05, Last modification date: 2024-05-15) |
Primary citation | Fu, Q.,Shaik, M.M.,Cai, Y.,Ghantous, F.,Piai, A.,Peng, H.,Rits-Volloch, S.,Liu, Z.,Harrison, S.C.,Seaman, M.S.,Chen, B.,Chou, J.J. Structure of the membrane proximal external region of HIV-1 envelope glycoprotein. Proc. Natl. Acad. Sci. U.S.A., 115:E8892-E8899, 2018 Cited by PubMed Abstract: The membrane-proximal external region (MPER) of the HIV-1 envelope glycoprotein (Env) bears epitopes of broadly neutralizing antibodies (bnAbs) from infected individuals; it is thus a potential vaccine target. We report an NMR structure of the MPER and its adjacent transmembrane domain in bicelles that mimic a lipid-bilayer membrane. The MPER lies largely outside the lipid bilayer. It folds into a threefold cluster, stabilized mainly by conserved hydrophobic residues and potentially by interaction with phospholipid headgroups. Antigenic analysis and comparison with published images from electron cryotomography of HIV-1 Env on the virion surface suggest that the structure may represent a prefusion conformation of the MPER, distinct from the fusion-intermediate state targeted by several well-studied bnAbs. Very slow bnAb binding indicates that infrequent fluctuations of the MPER structure give these antibodies occasional access to alternative conformations of MPER epitopes. Mutations in the MPER not only impede membrane fusion but also influence presentation of bnAb epitopes in other regions. These results suggest strategies for developing MPER-based vaccine candidates. PubMed: 30185554DOI: 10.1073/pnas.1807259115 PDB entries with the same primary citation |
Experimental method | SOLUTION NMR |
Structure validation
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