7nyd

cryoEM structure of 2C9-sMAC

spinqualitylabelsall models 7nyd, resolution 3.27Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 7nyd is a 8 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: Electron Microscopy, Resolution 3.27Å Ligands: BMA, CA, FUC, MAN, NAG Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Disease CO8A_HUMAN Defects in C8A are a cause of complement component 8 deficiency type 1 (C8D1) [MIM:613790. A rare defect of the complement classical pathway associated with susceptibility to severe recurrent infections, predominantly by Neisseria gonorrhoeae or Neisseria meningitidis. Function CO8A_HUMAN Constituent of the membrane attack complex (MAC) that plays a key role in the innate and adaptive immune response by forming pores in the plasma membrane of target cells. C8A inserts into the target membrane, but does not form pores by itself. Publication Abstract from PubMed 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 beta-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. Structural basis of soluble membrane attack complex packaging for clearance.,Menny A, Lukassen MV, Couves EC, Franc V, Heck AJR, Bubeck D Nat Commun. 2021 Oct 19;12(1):6086. doi: 10.1038/s41467-021-26366-w. PMID:34667172 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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