National Institutes of Health/National Institute Of Allergy and Infectious Diseases (NIH/NIAID)
米国
引用
ジャーナル: Commun Biol / 年: 2024 タイトル: Mechanism of complement inhibition by a mosquito protein revealed through cryo-EM. 著者: John F Andersen / Haotian Lei / Ethan C Strayer / Van Pham / José M C Ribeiro / 要旨: Salivary complement inhibitors occur in many of the blood feeding arthropod species responsible for transmission of pathogens. During feeding, these inhibitors prevent the production of ...Salivary complement inhibitors occur in many of the blood feeding arthropod species responsible for transmission of pathogens. During feeding, these inhibitors prevent the production of proinflammatory anaphylatoxins, which may interfere with feeding, and limit formation of the membrane attack complex which could damage arthropod gut tissues. Salivary inhibitors are, in many cases, novel proteins which may be pharmaceutically useful or display unusual mechanisms that could be exploited pharmaceutically. Albicin is a potent inhibitor of the alternative pathway of complement from the saliva of the malaria transmitting mosquito, Anopheles albimanus. Here we describe the cryo-EM structure of albicin bound to C3bBb, the alternative C3 convertase, a proteolytic complex that is responsible for cleavage of C3 and amplification of the complement response. Albicin is shown to induce dimerization of C3bBb, in a manner similar to the bacterial inhibitor SCIN, to form an inactive complex unable to bind the substrate C3. Size exclusion chromatography and structures determined after 30 minutes of incubation of C3b, factor B (FB), factor D (FD) and albicin indicate that FBb dissociates from the inhibited dimeric complex leaving a C3b-albicin dimeric complex which apparently decays more slowly.
名称: complex of C3bBb with the inhibitor albicin / タイプ: COMPLEX / Entity ID: #1-#4 / 由来: MULTIPLE SOURCES
分子量
実験値: NO
由来(天然)
生物種: Homo sapiens (ヒト)
緩衝液
pH: 7.4 / 詳細: 10 mM Hepes pH 7.4, 150 mM NaCl, 5 mM MgCl2
試料
濃度: 1.5 mg/ml / 包埋: NO / シャドウイング: NO / 染色: NO / 凍結: YES 詳細: The sample was formed by incubating C3b, factor B, factor D and albicin. The sample was monodisperse
試料支持
グリッドの材料: GOLD / グリッドのタイプ: C-flat-1.2/1.3
急速凍結
装置: FEI VITROBOT MARK III / 凍結剤: ETHANE / 湿度: 100 % / 凍結前の試料温度: 279.15 K