Structural basis for HCMV Pentamer receptor recognition and antibody neutralization.
Détails
Télécharger: sciadv.abm2536 (1).pdf (4271.94 [Ko])
Etat: Public
Version: de l'auteur⸱e
Licence: CC BY-NC 4.0
Etat: Public
Version: de l'auteur⸱e
Licence: CC BY-NC 4.0
ID Serval
serval:BIB_9AD2F453F4AF
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Institution
Titre
Structural basis for HCMV Pentamer receptor recognition and antibody neutralization.
Périodique
Science advances
ISSN
2375-2548 (Electronic)
ISSN-L
2375-2548
Statut éditorial
Publié
Date de publication
11/03/2022
Peer-reviewed
Oui
Volume
8
Numéro
10
Pages
eabm2536
Langue
anglais
Notes
Publication types: Journal Article
Publication Status: ppublish
Publication Status: ppublish
Résumé
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.
Mots-clé
Multidisciplinary
Pubmed
Web of science
Open Access
Oui
Financement(s)
Fonds national suisse / Projets / 310030_204679
Création de la notice
15/03/2022 9:42
Dernière modification de la notice
21/11/2022 8:23