2013年11月5日訊 /生物谷BIOON/--近日，Leicester科學家們繪製出人體免疫系統中負責中和細菌和病毒的關鍵組分的結構。Leicester大學科學家獲得一個大型複雜免疫系統（補體系統）中補體成分C1複合體的結構。
C1複合體是一種蛋白質，它負責發現血液中可能會導致疾病的病原體。當遇到細菌，病毒，真菌和其它入侵物質時啟動補體系統，刺激人體的免疫系統，包括膜攻擊複合物（MAC）蛋白質的激活，攻擊和殺死外來物質。
雖然，50多年前人們就已經發現C1複合體，但到現在為止，它的作用方式人們還是知之甚少。現在，研究人員發現了C1複合體的組成結構。在某些情況下，如心臟病發作或中風後，補體系統會攻擊自己的組織，防止身體恢復。了解C1複合體的結構可以幫助科學家開發抑制劑阻止補體系統。
這項研究揭示了C1複合體由補體組成C1q、C1r和C1s形成，C1q是負責識別病原體的亞成分。Russell Wallis博士說：我們已經確定了補體成分C1複合體的結構。這幫助我們了解我們自身的免疫系統，可以幫助我們開發治療方法以防止補體系統出錯。
新研究第一次揭示了C1複合體是如何組裝的，並揭示其是如何激活補體級聯反應的。這一發現有助於理解免疫系統如何預防疾病，從長遠來看，研究結果可能促進開發新的療法。舉個例子，一些疾病狀態如心臟病發作或中風發生後，補體系統攻擊我們自己組織。在這種情況下，補體抑制劑的使用可以防止這種損害的發生，讓身體恢復正常狀態。（生物谷Bioon.com）
Structural basis of the C1q/C1s interaction and its central role in assembly of the C1 complex of complement activation
Umakhanth Venkatraman Girija, et al.
Complement component C1, the complex that initiates the classical pathway of complement activation, is a 790-kDa assembly formed from the target-recognition subcomponent C1q and the modular proteases C1r and C1s. The proteases are elongated tetramers that become more compact when they bind to the collagen-like domains of C1q. Here, we describe a series of structures that reveal how the subcomponents associate to form C1. A complex between C1s and a collagen-like peptide containing the C1r/C1s-binding motif of C1q shows that the collagen binds to a shallow groove via a critical lysine side chain that contacts Ca2+-coordinating residues. The data explain the Ca2+-dependent binding mechanism, which is conserved in C1r and also in mannan-binding lectin-associated serine proteases, the serine proteases of the lectin pathway activation complexes. In an accompanying structure, C1s forms a compact ring-shaped tetramer featuring a unique head-to-tail interaction at its center that replicates the likely arrangement of C1r/C1s polypeptides in the C1 complex. Additional structures reveal how C1s polypeptides are positioned to enable activation by C1r and interaction with the substrate C4 inside the cage-like assembly formed by the collagenous stems of C1q. Together with previously determined structures of C1r fragments, the results reported here provide a structural basis for understanding the early steps of complement activation via the classical pathway.