7U0K

IOMA class antibody Fab ACS124

Summary for 7U0K

• Entry DOI: 10.2210/pdb7u0k/pdb
• Descriptor: IOMA Class antibody ACS124 Light chain, IOMA Class antibody ACS124 Heavy chain, 2-[N-CYCLOHEXYLAMINO]ETHANE SULFONIC ACID, ... (4 entities in total)
• Functional Keywords: hiv, immune system
• Biological source: Homo sapiens (Human); More
• Total number of polymer chains: 2
• Total formula weight: 47964.71

Authors

Farokhi, E.,Stanfield, R.L.,Wilson, I.A. (deposition date: 2022-02-18, release date: 2022-08-24, Last modification date: 2024-10-09)

Primary citation

van Schooten, J.,Farokhi, E.,Schorcht, A.,van den Kerkhof, T.L.G.M.,Gao, H.,van der Woude, P.,Burger, J.A.,Meesters, T.G.R.,Bijl, T.,Ghalaiyini, R.,Turner, H.L.,Dorning, J.,van Schaik, B.D.C.,van Kampen, A.H.C.,Labranche, C.C.,Stanfield, R.L.,Sok, D.,Montefiori, D.C.,Burton, D.R.,Seaman, M.S.,Ozorowski, G.,Wilson, I.A.,Sanders, R.W.,Ward, A.B.,van Gils, M.J.
Identification of IOMA-class neutralizing antibodies targeting the CD4-binding site on the HIV-1 envelope glycoprotein.
Nat Commun, 13:4515-4515, 2022

PubMed Abstract: A major goal of current HIV-1 vaccine design efforts is to induce broadly neutralizing antibodies (bNAbs). The VH1-2-derived bNAb IOMA directed to the CD4-binding site of the HIV-1 envelope glycoprotein is of interest because, unlike the better-known VH1-2-derived VRC01-class bNAbs, it does not require a rare short light chain complementarity-determining region 3 (CDRL3). Here, we describe three IOMA-class NAbs, ACS101-103, with up to 37% breadth, that share many characteristics with IOMA, including an average-length CDRL3. Cryo-electron microscopy revealed that ACS101 shares interactions with those observed with other VH1-2 and VH1-46-class bNAbs, but exhibits a unique binding mode to residues in loop D. Analysis of longitudinal sequences from the patient suggests that a transmitter/founder-virus lacking the N276 glycan might have initiated the development of these NAbs. Together these data strengthen the rationale for germline-targeting vaccination strategies to induce IOMA-class bNAbs and provide a wealth of sequence and structural information to support such strategies.

PubMed: 35922441
DOI: 10.1038/s41467-022-32208-0

Experimental method

X-RAY DIFFRACTION (1.73 Å)