5WDF

Crystal structure of 10E8v4-5R+100cF Fab in complex with HIV-1 gp41 peptide

5WDF の概要

• エントリーDOI: 10.2210/pdb5wdf/pdb
• 分子名称: 10E8v4-5R+100cF Fab heavy chain, FA10E8v4-5R+100cF FAB light chain, HIV-1 gp41 peptide (3 entities in total)
• 機能のキーワード: hiv-1 neutralizing antibody, mper, 10e8, immune system
• 由来する生物種: Homo sapiens (human); 詳細
• タンパク質・核酸の鎖数: 6
• 化学式量合計: 100758.42

構造登録者

Kwon, Y.D.,Kwong, P.D. (登録日: 2017-07-05, 公開日: 2018-03-21, 最終更新日: 2024-11-13)

主引用文献

Kwon, Y.D.,Chuang, G.Y.,Zhang, B.,Bailer, R.T.,Doria-Rose, N.A.,Gindin, T.S.,Lin, B.,Louder, M.K.,McKee, K.,O'Dell, S.,Pegu, A.,Schmidt, S.D.,Asokan, M.,Chen, X.,Choe, M.,Georgiev, I.S.,Jin, V.,Pancera, M.,Rawi, R.,Wang, K.,Chaudhuri, R.,Kueltzo, L.A.,Manceva, S.D.,Todd, J.P.,Scorpio, D.G.,Kim, M.,Reinherz, E.L.,Wagh, K.,Korber, B.M.,Connors, M.,Shapiro, L.,Mascola, J.R.,Kwong, P.D.
Surface-Matrix Screening Identifies Semi-specific Interactions that Improve Potency of a Near Pan-reactive HIV-1-Neutralizing Antibody.
Cell Rep, 22:1798-1809, 2018

PubMed Abstract: Highly effective HIV-1-neutralizing antibodies could have utility in the prevention or treatment of HIV-1 infection. To improve the potency of 10E8, an antibody capable of near pan-HIV-1 neutralization, we engineered 10E8-surface mutants and screened for improved neutralization. Variants with the largest functional enhancements involved the addition of hydrophobic or positively charged residues, which were positioned to interact with viral membrane lipids or viral glycan-sialic acids, respectively. In both cases, the site of improvement was spatially separated from the region of antibody mediating molecular contact with the protein component of the antigen, thereby improving peripheral semi-specific interactions while maintaining unmodified dominant contacts responsible for broad recognition. The optimized 10E8 antibody, with mutations to phenylalanine and arginine, retained the extraordinary breadth of 10E8 but with ∼10-fold increased potency. We propose surface-matrix screening as a general method to improve antibodies, with improved semi-specific interactions between antibody and antigen enabling increased potency without compromising breadth.

PubMed: 29444432
DOI: 10.1016/j.celrep.2018.01.023

実験手法

X-RAY DIFFRACTION (3.1 Å)