9BLX

Rhesus macaque ITS111.01 Fab in complex with SIV MPER peptide

Summary for 9BLX

• Entry DOI: 10.2210/pdb9blx/pdb
• Descriptor: ITS111.01 Heavy, ITS111.01 Light, Envelope glycoprotein gp160, ... (6 entities in total)
• Functional Keywords: fab, mper, membrane-proximal external region, hiv-1, gp41, immune system, siv, immune system-viral protein complex, immune system/viral protein
• Biological source: Macaca mulatta; More
• Total number of polymer chains: 6
• Total formula weight: 103315.07

Authors

Gorman, J.,Ahmadi, M.,Kwong, P.D. (deposition date: 2024-05-02, release date: 2025-01-15, Last modification date: 2025-01-22)

Primary citation

Gorman, J.,Du, R.,Lai, Y.T.,Ahmadi, M.S.,King, H.A.D.,Song, K.,Manalang, K.,Gonelli, C.A.,Schramm, C.A.,Cheng, C.,Nguyen, R.,Ambrozak, D.,Druz, A.,Shen, C.H.,Yang, Y.,Douek, D.C.,Kwong, P.D.,Roederer, M.,Mason, R.D.
Isolation and structure of broad SIV-neutralizing antibodies reveal a proximal helical MPER epitope recognized by a rhesus multi-donor class.
Cell Rep, 44:115163-115163, 2025

PubMed Abstract: The membrane-proximal external region (MPER) of the HIV-1 envelope is a target for broadly neutralizing antibodies (bnAbs), and vaccine-elicited MPER-directed antibodies have recently been reported from a human clinical trial. In this study, we sought to identify MPER-directed nAbs in simian immunodeficiency virus (SIV)-infected rhesus macaques. We isolated four lineages of SIV MPER-directed nAbs from two SIV-infected macaques. The nAbs displayed low potency but up to 90% breadth on a 20-strain SIV panel. Crystal structures of representative nAbs in complex with SIV MPER peptides revealed the SIV antibodies to bind a helical epitope at the N-terminal (proximal) region of the MPER, defining a reproducible multi-donor class encompassing all four lineages. HIV-1 comparison showed that this class of SIV MPER-directed antibodies targets a helical region overlapping that targeted by human vaccine-elicited ones. Thus, a prevalent and reproducible class of SIV bnAbs recognizes an epitope similar to that recently observed in an HIV-1-vaccine trial.

PubMed: 39792559
DOI: 10.1016/j.celrep.2024.115163

Experimental method

X-RAY DIFFRACTION (1.96 Å)