Regulation of multiple dimeric states of E-cadherin by adhesion activating antibodies revealed through Cryo-EM and X-ray crystallography.
Journal
PNAS nexus
ISSN: 2752-6542
Titre abrégé: PNAS Nexus
Pays: England
ID NLM: 9918367777906676
Informations de publication
Date de publication:
Sep 2022
Sep 2022
Historique:
received:
05
05
2022
accepted:
15
08
2022
entrez:
26
9
2022
pubmed:
27
9
2022
medline:
27
9
2022
Statut:
epublish
Résumé
E-cadherin adhesion is regulated at the cell surface, a process that can be replicated by activating antibodies. We use cryo-electron microscopy (EM) and X-ray crystallography to examine functional states of the cadherin adhesive dimer. This dimer is mediated by N-terminal beta strand-swapping involving Trp2, and forms via a different transient X-dimer intermediate. X-dimers are observed in cryo-EM along with monomers and strand-swap dimers, indicating that X-dimers form stable interactions. A novel EC4-mediated dimer was also observed. Activating Fab binding caused no gross structural changes in E-cadherin monomers, but can facilitate strand swapping. Moreover, activating Fab binding is incompatible with the formation of the X-dimer. Both cryo-EM and X-ray crystallography reveal a distinctive twisted strand-swap dimer conformation caused by an outward shift in the N-terminal beta strand that may represent a strengthened state. Thus, regulation of adhesion involves changes in cadherin dimer configurations.
Identifiants
pubmed: 36157596
doi: 10.1093/pnasnexus/pgac163
pii: pgac163
pmc: PMC9491697
doi:
Types de publication
Journal Article
Langues
eng
Pagination
pgac163Subventions
Organisme : NIAID NIH HHS
ID : HHSN272201700059C
Pays : United States
Organisme : NIGMS NIH HHS
ID : R35 GM122467
Pays : United States
Informations de copyright
© The Author(s) 2022. Published by Oxford University Press on behalf of National Academy of Sciences.
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