4XC1

Crystal structure of human 4E10 Fab in complex with its peptide epitope on HIV-1 GP41: crystals cryoprotected with sn-Glycerol 3-phosphate

4XC1 の概要

• エントリーDOI: 10.2210/pdb4xc1/pdb
• 関連するPDBエントリー: 4XAW 4XBE 4XBG 4XBP 4XC3 4XCC 4XCE 4XCF 4XCN 4XCY
• 分子名称: 4E10 FAB LIGHT CHAIN, 4E10 FAB HEAVY CHAIN, MODIFIED FRAGMENT OF HIV-1 GLYCOPROTEIN (GP41) INCLUDING THE MPER REGION 671-683, ... (6 entities in total)
• 機能のキーワード: hiv-1 gp41 mper, 4e10 fab, lipid membrane, immune system
• 由来する生物種: Homo sapiens; 詳細
• タンパク質・核酸の鎖数: 3
• 化学式量合計: 50422.40

構造登録者

Irimia, A.,Stanfield, R.L.,Wilson, I.A. (登録日: 2014-12-17, 公開日: 2016-02-03, 最終更新日: 2023-11-15)

主引用文献

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

実験手法

X-RAY DIFFRACTION (1.63 Å)