Insights into IgM-mediated complement activation based on in situ structures of IgM-C1-C4b.
C1
IgM
complement
cryoelectron tomography
subtomogram averaging
Journal
Proceedings of the National Academy of Sciences of the United States of America
ISSN: 1091-6490
Titre abrégé: Proc Natl Acad Sci U S A
Pays: United States
ID NLM: 7505876
Informations de publication
Date de publication:
11 06 2019
11 06 2019
Historique:
pubmed:
31
5
2019
medline:
21
3
2020
entrez:
1
6
2019
Statut:
ppublish
Résumé
Antigen binding by serum Ig-M (IgM) protects against microbial infections and helps to prevent autoimmunity, but causes life-threatening diseases when mistargeted. How antigen-bound IgM activates complement-immune responses remains unclear. We present cryoelectron tomography structures of IgM, C1, and C4b complexes formed on antigen-bearing lipid membranes by normal human serum at 4 °C. The IgM-C1-C4b complexes revealed C4b product release as the temperature-limiting step in complement activation. Both IgM hexamers and pentamers adopted hexagonal, dome-shaped structures with Fab pairs, dimerized by hinge domains, bound to surface antigens that support a platform of Fc regions. C1 binds IgM through widely spread C1q-collagen helices, with C1r proteases pointing outward and C1s bending downward and interacting with surface-attached C4b, which further interacts with the adjacent IgM-Fab
Identifiants
pubmed: 31147461
pii: 1901841116
doi: 10.1073/pnas.1901841116
pmc: PMC6575175
doi:
Substances chimiques
Antibodies
0
Antigens
0
Complement C1
0
Complement C4
0
Immunoglobulin M
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
11900-11905Informations de copyright
Copyright © 2019 the Author(s). Published by PNAS.
Déclaration de conflit d'intérêts
The authors declare no conflict of interest.
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