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-Structure paper
Title | Structural basis for HCMV Pentamer receptor recognition and antibody neutralization. |
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Journal, issue, pages | Sci Adv, Vol. 8, Issue 10, Page eabm2536, Year 2022 |
Publish date | Mar 11, 2022 |
Authors | Marc Kschonsak / Matthew C Johnson / Rachel Schelling / Evan M Green / Lionel Rougé / Hoangdung Ho / Nidhi Patel / Cem Kilic / Edward Kraft / Christopher P Arthur / Alexis L Rohou / Laetitia Comps-Agrar / Nadia Martinez-Martin / Laurent Perez / Jian Payandeh / Claudio Ciferri / |
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 ...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. |
External links | Sci Adv / PubMed:35275719 / PubMed Central |
Methods | EM (single particle) |
Resolution | 2.9 - 3.84 Å |
Structure data | EMDB-25685, PDB-7t4q: EMDB-25686, PDB-7t4r: EMDB-25687, PDB-7t4s: EMDB-25688: CryoEM structure of 2x HCMV Pentamer gH/gL/UL128/UL130/UL131A in complex with NRP2 and 2x neutralizing fabs 8I21 and 13H11 |
Chemicals | ChemComp-NAG: ChemComp-CA: |
Source |
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Keywords | VIRAL PROTEIN/Immune System / Human Cytomegalovirus / glycoprotein complex / antibody complex / VIRAL PROTEIN / VIRAL PROTEIN-Immune System complex / thrombomodulin / Neuropilin 2 |