Advances in cryo-EM that have shaped mechanistic models of membrane attack complex assembly and regulation
File(s)
Published version
Author(s)
Noone, Dylan P
Bubeck, Doryen
Type
Journal Article
Abstract
The complement system is a blood-based immune network that plays a crucial role in fighting infection and maintaining immune homeostasis. The membrane attack
complex (MAC) is a pore assembled from complement proteins that creates holes in cells when the immune system is activated. Over the last 10 years, advances in cryo electron microscopy (cryo-EM) have enabled key molecular insights into how MAC assembles, remodels membranes, and is regulated. These new tools revealed the inherent flexibility of complement complexes. By adapting computational approaches that disentangle diverse conformations, these studies have provided detailed mechanisms for MAC activity that could underpin novel complement-targeted therapeutics. Now accelerated by AI-driven image analysis and advances in structural cell biology, the next revolution in cryo-EM o ers new opportunities to understand the cellular consequences of immune activation.
complex (MAC) is a pore assembled from complement proteins that creates holes in cells when the immune system is activated. Over the last 10 years, advances in cryo electron microscopy (cryo-EM) have enabled key molecular insights into how MAC assembles, remodels membranes, and is regulated. These new tools revealed the inherent flexibility of complement complexes. By adapting computational approaches that disentangle diverse conformations, these studies have provided detailed mechanisms for MAC activity that could underpin novel complement-targeted therapeutics. Now accelerated by AI-driven image analysis and advances in structural cell biology, the next revolution in cryo-EM o ers new opportunities to understand the cellular consequences of immune activation.
Date Issued
2026-05-01
Date Acceptance
2026-03-19
Citation
IUCrJ, 2026, 13 (Part 3), pp.221-227
ISSN
2052-2525
Publisher
International Union of Crystallography
Start Page
221
End Page
227
Journal / Book Title
IUCrJ
Volume
13
Issue
Part 3
Copyright Statement
© The Author(s) 2026. This is an open-access article distributed under the terms of the Creative Commons Attribution (CC-BY) Licence, which permits unrestricted use, distribution, and reproduction in any medium, provided the original authors and source are cited.
License URL
Identifier
10.1107/S2052252526002927
Subjects
cryo-EM
complement
membrane attack complexes
CD59. Supporting information: this article has supporting information at www.iucrj.org
Publication Status
Published
Date Publish Online
2026-04-23