7NYC

cryoEM structure of 3C9-sMAC

Summary for 7NYC

• Entry DOI: 10.2210/pdb7nyc/pdb
• Related: 7NYD
• EMDB information: 12646 12647 12648 12649 12650 12651
• Descriptor: Complement component C7, alpha-D-mannopyranose, CALCIUM ION, ... (13 entities in total)
• Functional Keywords: complement, macpf, membrane attack complex, cdc, pore forming, immune system
• Biological source: Homo sapiens (Human); More
• Total number of polymer chains: 9
• Total formula weight: 710236.44

Authors

Menny, A.,Couves, E.C.,Bubeck, D. (deposition date: 2021-03-22, release date: 2021-10-06, Last modification date: 2024-11-20)

Primary citation

Menny, A.,Lukassen, M.V.,Couves, E.C.,Franc, V.,Heck, A.J.R.,Bubeck, D.
Structural basis of soluble membrane attack complex packaging for clearance.
Nat Commun, 12:6086-6086, 2021

PubMed Abstract: Unregulated complement activation causes inflammatory and immunological pathologies with consequences for human disease. To prevent bystander damage during an immune response, extracellular chaperones (clusterin and vitronectin) capture and clear soluble precursors to the membrane attack complex (sMAC). However, how these chaperones block further polymerization of MAC and prevent the complex from binding target membranes remains unclear. Here, we address that question by combining cryo electron microscopy (cryoEM) and cross-linking mass spectrometry (XL-MS) to solve the structure of sMAC. Together our data reveal how clusterin recognizes and inhibits polymerizing complement proteins by binding a negatively charged surface of sMAC. Furthermore, we show that the pore-forming C9 protein is trapped in an intermediate conformation whereby only one of its two transmembrane β-hairpins has unfurled. This structure provides molecular details for immune pore formation and helps explain a complement control mechanism that has potential implications for how cell clearance pathways mediate immune homeostasis.

PubMed: 34667172
DOI: 10.1038/s41467-021-26366-w

Experimental method

ELECTRON MICROSCOPY (3.54 Å)