7T4S

CryoEM structure of the HCMV Pentamer gH/gL/UL128/UL130/UL131A in complex with NRP2 and neutralizing fabs 8I21 and 13H11

Summary for 7T4S

• Entry DOI: 10.2210/pdb7t4s/pdb
• EMDB information: 25687
• Descriptor: Envelope glycoprotein H, Fab 8I21 light chain, 2-acetamido-2-deoxy-beta-D-glucopyranose, ... (12 entities in total)
• Functional Keywords: glycoprotein complex, antibody complex, neuropilin 2, viral protein, viral protein-immune system complex, viral protein/immune system
• Biological source: Human betaherpesvirus 5; More
• Total number of polymer chains: 10
• Total formula weight: 387927.30

Authors

Kschonsak, M.,Johnson, M.C.,Schelling, R.,Green, E.M.,Rouge, L.,Ho, H.,Patel, N.,Kilic, C.,Kraft, E.,Arthur, C.P.,Rohou, A.L.,Comps-Agrar, L.,Martinez-Martin, N.,Perez, L.,Payandeh, J.,Ciferri, C. (deposition date: 2021-12-10, release date: 2022-03-23, Last modification date: 2024-10-30)

Primary citation

Kschonsak, M.,Johnson, M.C.,Schelling, R.,Green, E.M.,Rouge, L.,Ho, H.,Patel, N.,Kilic, C.,Kraft, E.,Arthur, C.P.,Rohou, A.L.,Comps-Agrar, L.,Martinez-Martin, N.,Perez, L.,Payandeh, J.,Ciferri, C.
Structural basis for HCMV Pentamer receptor recognition and antibody neutralization.
Sci Adv, 8:eabm2536-eabm2536, 2022

PubMed Abstract: Human cytomegalovirus (HCMV) represents the viral leading cause of congenital birth defects and uses the gH/gL/UL128-130-131A complex (Pentamer) to enter different cell types, including epithelial and endothelial cells. Upon infection, Pentamer elicits the most potent neutralizing response against HCMV, representing a key vaccine candidate. Despite its relevance, the structural basis for Pentamer receptor recognition and antibody neutralization is largely unknown. Here, we determine the structures of Pentamer bound to neuropilin 2 (NRP2) and a set of potent neutralizing antibodies against HCMV. Moreover, we identify thrombomodulin (THBD) as a functional HCMV receptor and determine the structures of the Pentamer-THBD complex. Unexpectedly, both NRP2 and THBD also promote dimerization of Pentamer. Our results provide a framework for understanding HCMV receptor engagement, cell entry, antibody neutralization, and outline strategies for antiviral therapies against HCMV.

PubMed: 35275719
DOI: 10.1126/sciadv.abm2536

Experimental method

ELECTRON MICROSCOPY (3.1 Å)