4LRI

Anti CMV Fab Fragment

Summary for 4LRI

• Entry DOI: 10.2210/pdb4lri/pdb
• Descriptor: MSL-109 Light Chain, MSL-109 Heavy Chain (3 entities in total)
• Functional Keywords: fab fragment, cmv neutralizing antibody, glycoprotein h or gh from cmv, immune system
• Biological source: Homo sapiens; More
• Total number of polymer chains: 4
• Total formula weight: 97806.85

Authors

Stengel, K.F. (deposition date: 2013-07-19, release date: 2014-05-21, Last modification date: 2024-11-20)

Primary citation

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

Experimental method

X-RAY DIFFRACTION (1.65 Å)