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Structure of C8a-MACPF reveals mechanism of membrane attack in complement immune defenseStructure of C8a-MACPF reveals mechanism of membrane attack in complement immune defense
Structural highlights
DiseaseCO8A_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. FunctionCO8A_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.[1] [2] Evolutionary Conservation![]() Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf. Publication Abstract from PubMedMembrane attack is important for mammalian immune defense against invading microorganisms and infected host cells. Proteins of the complement membrane attack complex (MAC) and the protein perforin share a common MACPF domain that is responsible for membrane insertion and pore formation. We determined the crystal structure of the MACPF domain of complement component C8alpha at 2.5 angstrom resolution and show that it is structurally homologous to the bacterial, pore-forming, cholesterol-dependent cytolysins. The structure displays two regions that (in the bacterial cytolysins) refold into transmembrane beta hairpins, forming the lining of a barrel pore. Local hydrophobicity explains why C8alpha is the first complement protein to insert into the membrane. The size of the MACPF domain is consistent with known C9 pore sizes. These data imply that these mammalian and bacterial cytolytic proteins share a common mechanism of membrane insertion. Structure of C8alpha-MACPF reveals mechanism of membrane attack in complement immune defense.,Hadders MA, Beringer DX, Gros P Science. 2007 Sep 14;317(5844):1552-4. PMID:17872444[3] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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