3K9A

Crystal Structure of HIV gp41 with MPER

Summary for 3K9A

• Entry DOI: 10.2210/pdb3k9a/pdb
• Descriptor: HIV glycoprotein gp41 (2 entities in total)
• Functional Keywords: hiv, gp41, membrane proximal external region, mper, viral protein
• Biological source: Human immunodeficiency virus 1
• Total number of polymer chains: 1
• Total formula weight: 12722.10

Authors

Shi, W.,Han, D.,Habte, H.,Cho, M.,Chance, M.R. (deposition date: 2009-10-15, release date: 2010-05-26, Last modification date: 2023-09-06)

Primary citation

Shi, W.,Bohon, J.,Han, D.P.,Habte, H.,Qin, Y.,Cho, M.W.,Chance, M.R.
Structural characterization of HIV gp41 with the membrane-proximal external region
J.Biol.Chem., 285:24290-24298, 2010

PubMed Abstract: Human immunodeficiency virus, type 1 (HIV-1) envelope glycoprotein (gp120/gp41) plays a critical role in virus infection and pathogenesis. Three of the six monoclonal antibodies considered to have broadly neutralizing activities (2F5, 4E10, and Z13e1) bind to the membrane-proximal external region (MPER) of gp41. This makes the MPER a desirable template for developing immunogens that can elicit antibodies with properties similar to these monoclonal antibodies, with a long term goal of developing antigens that could serve as novel HIV vaccines. In order to provide a structural basis for rational antigen design, an MPER construct, HR1-54Q, was generated for x-ray crystallographic and x-ray footprinting studies to provide both high resolution atomic coordinates and verification of the solution state of the antigen, respectively. The crystal structure of HR1-54Q reveals a trimeric, coiled-coil six-helical bundle, which probably represents a postfusion form of gp41. The MPER portion extends from HR2 in continuation of a slightly bent long helix and is relatively flexible. The structures observed for the 2F5 and 4E10 epitopes agree well with existing structural data, and enzyme-linked immunosorbent assays indicate that the antigen binds well to antibodies that recognize the above epitopes. Hydroxyl radical-mediated protein footprinting of the antigen in solution reveals specifically protected and accessible regions consistent with the predictions based on the trimeric structure from the crystallographic data. Overall, the HR1-54Q antigen, as characterized by crystallography and footprinting, represents a postfusion, trimeric form of HIV gp41, and its structure provides a rational basis for gp41 antigen design suitable for HIV vaccine development.

PubMed: 20525690
DOI: 10.1074/jbc.M110.111351

Experimental method

X-RAY DIFFRACTION (2.1 Å)