Structure of human complement C8, a precursor to membrane attack

Bubeck, Doryen, Roversi, Pietro, Donev, Rossen Mintchev, Morgan, Bryan Paul ORCID: https://orcid.org/0000-0003-4075-7676, Llorca, Oscar and Lea, Susan M. 2011. Structure of human complement C8, a precursor to membrane attack. Journal of Molecular Biology 405 (2) , pp. 325-330. 10.1016/j.jmb.2010.10.031

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Abstract

Complement component C8 plays a pivotal role in the formation of the membrane attack complex (MAC), an important antibacterial immune effector. C8 initiates membrane penetration and coordinates MAC pore formation. High-resolution structures of C8 subunits have provided some insight into the function of the C8 heterotrimer; however, there is no structural information describing how the intersubunit organization facilitates MAC assembly. We have determined the structure of C8 by electron microscopy and fitted the C8α-MACPF (membrane attack complex/perforin)-C8γ co-crystal structure and a homology model for C8β-MACPF into the density. Here, we demonstrate that both the C8γ protrusion and the C8α-MACPF region that inserts into the membrane upon activation are accessible.

Item Type:	Article
Date Type:	Publication
Status:	Published
Schools:	Schools > Medicine
Subjects:	Q Science > QR Microbiology > QR180 Immunology R Medicine > RB Pathology
Uncontrolled Keywords:	C8, complement, 3D electron microscopy, terminal pathway, membrane attack complex (MAC)
Publisher:	Elsevier
ISSN:	0022-2836
Last Modified:	20 Oct 2022 07:40
URI:	https://orca.cardiff.ac.uk/id/eprint/26020

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