4LRI

Anti CMV Fab Fragment

4LRI の概要

• エントリーDOI: 10.2210/pdb4lri/pdb
• 分子名称: MSL-109 Light Chain, MSL-109 Heavy Chain (3 entities in total)
• 機能のキーワード: fab fragment, cmv neutralizing antibody, glycoprotein h or gh from cmv, immune system
• 由来する生物種: Homo sapiens; 詳細
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 97806.85

構造登録者

Stengel, K.F. (登録日: 2013-07-19, 公開日: 2014-05-21, 最終更新日: 2024-11-20)

主引用文献

Fouts, A.E.,Comps-Agrar, L.,Stengel, K.F.,Ellerman, D.,Schoeffler, A.J.,Warming, S.,Eaton, D.L.,Feierbach, B.
Mechanism for neutralizing activity by the anti-CMV gH/gL monoclonal antibody MSL-109.
Proc.Natl.Acad.Sci.USA, 111:8209-8214, 2014

PubMed Abstract: Cytomegalovirus (CMV) is a widespread opportunistic pathogen that causes birth defects when transmitted transplacentally and severe systemic illness in immunocompromised individuals. MSL-109, a human monoclonal IgG isolated from a CMV seropositive individual, binds to the essential CMV entry glycoprotein H (gH) and prevents infection of cells. Here, we suggest a mechanism for neutralization activity by MSL-109. We define a genetic basis for resistance to MSL-109 and have generated a structural model of gH that reveals the epitope of this neutralizing antibody. Using surface-based, time-resolved FRET, we demonstrate that gH/gL interacts with glycoprotein B (gB). Additionally, we detect homodimers of soluble gH/gL heterodimers and confirm this novel oligomeric assembly on full-length gH/gL expressed on the cell surface. We show that MSL-109 perturbs the dimerization of gH/gL:gH/gL, suggesting that dimerization of gH/gL may be required for infectivity. gH/gL homodimerization may be conserved between alpha- and betaherpesviruses, because both CMV and HSV gH/gL demonstrate self-association in the FRET system. This study provides evidence for a novel mechanism of action for MSL-109 and reveals a previously undescribed aspect of viral entry that may be susceptible to therapeutic intervention.

PubMed: 24843144
DOI: 10.1073/pnas.1404653111

実験手法

X-RAY DIFFRACTION (1.65 Å)