The crystal structure of iC3b-CR3 αI reveals a modular recognition of the main opsonin iC3b by the CR3 integrin receptor.
Journal
Nature communications
ISSN: 2041-1723
Titre abrégé: Nat Commun
Pays: England
ID NLM: 101528555
Informations de publication
Date de publication:
12 04 2022
12 04 2022
Historique:
received:
05
10
2020
accepted:
15
03
2022
entrez:
13
4
2022
pubmed:
14
4
2022
medline:
15
4
2022
Statut:
epublish
Résumé
Complement activation on cell surfaces leads to the massive deposition of C3b, iC3b, and C3dg, the main complement opsonins. Recognition of iC3b by complement receptor type 3 (CR3) fosters pathogen opsonophagocytosis by macrophages and the stimulation of adaptive immunity by complement-opsonized antigens. Here, we present the crystallographic structure of the complex between human iC3b and the von Willebrand A inserted domain of the α chain of CR3 (αI). The crystal contains two composite interfaces for CR3 αI, encompassing distinct sets of contiguous macroglobulin (MG) domains on the C3c moiety, MG1-MG2 and MG6-MG7 domains. These composite binding sites define two iC3b-CR3 αI complexes characterized by specific rearrangements of the two semi-independent modules, C3c moiety and TED domain. Furthermore, we show the structure of iC3b in a physiologically-relevant extended conformation. Based on previously available data and novel insights reported herein, we propose an integrative model that reconciles conflicting facts about iC3b structure and function and explains the molecular basis for iC3b selective recognition by CR3 on opsonized surfaces.
Identifiants
pubmed: 35413960
doi: 10.1038/s41467-022-29580-2
pii: 10.1038/s41467-022-29580-2
pmc: PMC9005620
doi:
Substances chimiques
CD11b Antigen
0
Macrophage-1 Antigen
0
Opsonin Proteins
0
Complement C3b
80295-43-8
Complement System Proteins
9007-36-7
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
1955Informations de copyright
© 2022. The Author(s).
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