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6E8W

MPER-TM Domain of HIV-1 envelope glycoprotein (Env)

Summary for 6E8W
Entry DOI10.2210/pdb6e8w/pdb
NMR InformationBMRB: 30503
DescriptorEnvelope glycoprotein gp160 (1 entity in total)
Functional Keywordsmper-tmd hiv-1 env gp41, viral protein
Biological sourceHuman immunodeficiency virus 1
Total number of polymer chains3
Total formula weight18538.12
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 citationFu, 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: 30185554
DOI: 10.1073/pnas.1807259115
PDB entries with the same primary citation
Experimental method
SOLUTION NMR
Structure validation

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