3FN0
Crystal structure of HIV-1 neutralizing human Fab Z13e1 in complex with a 12-residue peptide containing the Z13e1 epitope on gp41
Summary for 3FN0
| Entry DOI | 10.2210/pdb3fn0/pdb |
| Descriptor | Fab Z13e1, Envelope polyprotein gp160, ... (4 entities in total) |
| Functional Keywords | z13e1, z13, hiv, env, gp41, immune system |
| Biological source | Homo sapiens More |
| Total number of polymer chains | 3 |
| Total formula weight | 49074.92 |
| Authors | Pejchal, R.,Wilson, I.A.,Zwick, M.B. (deposition date: 2008-12-22, release date: 2009-06-23, Last modification date: 2024-10-30) |
| Primary citation | Pejchal, R.,Gach, J.S.,Brunel, F.M.,Cardoso, R.M.,Stanfield, R.L.,Dawson, P.E.,Burton, D.R.,Zwick, M.B.,Wilson, I.A. A conformational switch in human immunodeficiency virus gp41 revealed by the structures of overlapping epitopes recognized by neutralizing antibodies. J.Virol., 83:8451-8462, 2009 Cited by PubMed Abstract: The membrane-proximal external region (MPER) of the human immunodeficiency virus (HIV) envelope glycoprotein (gp41) is critical for viral fusion and infectivity and is the target of three of the five known broadly neutralizing HIV type 1 (HIV-1) antibodies, 2F5, Z13, and 4E10. Here, we report the crystal structure of the Fab fragment of Z13e1, an affinity-enhanced variant of monoclonal antibody Z13, in complex with a 12-residue peptide corresponding to the core epitope (W(670)NWFDITN(677)) at 1.8-A resolution. The bound peptide adopts an S-shaped conformation composed of two tandem, perpendicular helical turns. This conformation differs strikingly from the alpha-helical structure adopted by an overlapping MPER peptide bound to 4E10. Z13e1 binds to an elbow in the MPER at the membrane interface, making relatively few interactions with conserved aromatics (Trp672 and Phe673) that are critical for 4E10 recognition. The comparison of the Z13e1 and 4E10 epitope structures reveals a conformational switch such that neutralization can occur by the recognition of the different conformations and faces of the largely amphipathic MPER. The Z13e1 structure provides significant new insights into the dynamic nature of the MPER, which likely is critical for membrane fusion, and it has significant implications for mechanisms of HIV-1 neutralization by MPER antibodies and for the design of HIV-1 immunogens. PubMed: 19515770DOI: 10.1128/JVI.00685-09 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (1.8 Å) |
Structure validation
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