荷蘭科學(xué)家最近成功“凍結(jié)”進(jìn)行中的免疫反應(yīng),,用于免疫學(xué)研究,。
補(bǔ)體系統(tǒng)是最古老的機(jī)體抵御異物的免疫反應(yīng)之一,。補(bǔ)體系統(tǒng)是天然免疫反應(yīng),沒有特異性,,利用一連串的蛋白質(zhì)反應(yīng)消滅病原體和細(xì)胞,。自身免疫系統(tǒng)變態(tài)反應(yīng)也通常與補(bǔ)體系統(tǒng)有關(guān)。
在進(jìn)行一個(gè)連續(xù)反應(yīng)體系研究時(shí),,我們需要查明每步反應(yīng)的詳細(xì)情況才能把握整個(gè)反應(yīng)體系,。科學(xué)家最新發(fā)明了一種金黃葡萄球菌補(bǔ)體抑制蛋白(SCIN)的方法可以使反應(yīng)體系停滯在一步特定反應(yīng),。通過凍結(jié)免疫反應(yīng),,研究人員可以研究反應(yīng)體系中蛋白質(zhì)復(fù)合體的結(jié)構(gòu),蛋白質(zhì)間如何結(jié)合,,每一步反應(yīng)在反應(yīng)體系中的作用等,。
通過利用SCIN,研究人員發(fā)現(xiàn)了正常細(xì)胞不會受到補(bǔ)體系統(tǒng)攻擊的機(jī)制,。H因子是保證補(bǔ)體系統(tǒng)不攻擊正常細(xì)胞的重要因素,。通過分析研究人員發(fā)現(xiàn),H因子可與正常細(xì)胞結(jié)合使補(bǔ)體系統(tǒng)不被激活,,從而使正常細(xì)胞不受補(bǔ)體系統(tǒng)攻擊,。(生物谷Bioon.com)
生物谷推薦原始出處:
Nature Immunology 10, 721 - 727 (2009) 7 June 2009 | doi:10.1038/ni.1756
Structural and functional implications of the alternative complement pathway C3 convertase stabilized by a staphylococcal inhibitor
Suzan H M Rooijakkers1,5, Jin Wu2,5, Maartje Ruyken1, Robert van Domselaar1, Karel L Planken3, Apostolia Tzekou4, Daniel Ricklin4, John D Lambris4, Bert J C Janssen2, Jos A G van Strijp1 & Piet Gros2
Abstract
Activation of the complement system generates potent chemoattractants and leads to the opsonization of cells for immune clearance. Short-lived protease complexes cleave complement component C3 into anaphylatoxin C3a and opsonin C3b. Here we report the crystal structure of the C3 convertase formed by C3b and the protease fragment Bb, which was stabilized by the bacterial immune-evasion protein SCIN. The data suggest that the proteolytic specificity and activity depend on the formation of dimers of C3 with C3b of the convertase. SCIN blocked the formation of a productive enzyme-substrate complex. Irreversible dissociation of the complex of C3b and Bb is crucial to complement regulation and was determined by slow binding kinetics of the Mg2+-adhesion site in Bb. Understanding the mechanistic basis of the central complement-activation step and microbial immune evasion strategies targeting this step will aid in the development of complement therapeutics.
1 Medical Microbiology, University Medical Center Utrecht, Utrecht, The Netherlands.
2 Crystal and Structural Chemistry, Bijvoet Center for Biomolecular Research, Department of Chemistry, Faculty of Science, Utrecht University, Utrecht, The Netherlands.
3 Van 't Hoff Laboratory for Physical and Colloid Chemistry, Utrecht University, Utrecht, The Netherlands.
4 Department of Pathology & Laboratory Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA.
5 These authors contributed equally to this work.