4XBG

Crystal structure of human 4E10 Fab in complex with phosphatidic acid (06:0 PA): 2.73 A resolution

Summary for 4XBG

• Entry DOI: 10.2210/pdb4xbg/pdb
• Related: 4XAW 4XBE 4XBP 4XC1 4XC3 4XCC 4XCE 4XCF 4XCN 4XCY
• Descriptor: 4E10 Fab light chain, 4E10 Fab heavy chain, UNKNOWN LIGAND, ... (7 entities in total)
• Functional Keywords: human anti gp41 hiv-1 4e10 fab, membrane lipid, phosphatidic acid, immune system
• Biological source: Homo sapiens; More
• Total number of polymer chains: 12
• Total formula weight: 287125.75

Authors

Irimia, A.,Stanfield, R.L.,Wilson, I.A. (deposition date: 2014-12-16, release date: 2016-02-03, Last modification date: 2024-10-23)

Primary citation

Irimia, A.,Sarkar, A.,Stanfield, R.L.,Wilson, I.A.
Crystallographic Identification of Lipid as an Integral Component of the Epitope of HIV Broadly Neutralizing Antibody 4E10.
Immunity, 44:21-31, 2016

PubMed Abstract: Numerous studies of the anti-HIV-1 envelope glycoprotein 41 (gp41) broadly neutralizing antibody 4E10 suggest that 4E10 also interacts with membrane lipids, but the antibody regions contacting lipids and its orientation with respect to the viral membrane are unknown. Vaccine immunogens capable of re-eliciting these membrane proximal external region (MPER)-like antibodies may require a lipid component to be successful. We performed a systematic crystallographic study of lipid binding to 4E10 to identify lipids bound by the antibody and the lipid-interacting regions. We identified phosphatidic acid, phosphatidylglycerol, and glycerol phosphate as specific ligands for 4E10 in the crystal structures. 4E10 used its CDRH1 loop to bind the lipid head groups, while its CDRH3 interacted with the hydrophobic lipid tails. Identification of the lipid binding sites on 4E10 may aid design of immunogens for vaccines that include a lipid component in addition to the MPER on gp41 for generation of broadly neutralizing antibodies.

PubMed: 26777395
DOI: 10.1016/j.immuni.2015.12.001

Experimental method

X-RAY DIFFRACTION (2.73 Å)