4WY7

Crystal structure of recombinant 4E10 expressed in Escherichia coli with epitope bound

Summary for 4WY7

• Entry DOI: 10.2210/pdb4wy7/pdb
• Related: 2FX7
• Descriptor: Fab 4E10 Heavy chain, Fab 4E10Light chain, Envelope glycoprotein gp160, ... (5 entities in total)
• Functional Keywords: broad neutralizing antobody, recombinant fab, epitope, immune system
• Biological source: Homo sapiens; More
• Cellular location: Transmembrane protein gp41: Virion membrane; Single-pass type I membrane protein. Surface protein gp120: Virion membrane; Peripheral membrane protein: P05880
• Total number of polymer chains: 3
• Total formula weight: 49654.50

Authors

Rujas, E.,Morante, K.,Tsumoto, K.,Nieva, J.L.,Caaveiro, J.M.M. (deposition date: 2014-11-16, release date: 2015-03-25, Last modification date: 2024-11-06)

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

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: 25787074
DOI: 10.1074/jbc.M115.644351

Experimental method

X-RAY DIFFRACTION (2.1 Å)