Kilchherr E, Hofmann H, Steigemann W, Engel J
J Mol Biol. 1985 Nov 20;186(2):403-15. doi: 10.1016/0022-2836(85)90114-7.
A detailed three-dimensional model of the collagenous part of C1q was derived by model building and computer-aided energy refinement calculations. The proposed structure is based on the collagen-like (-Gly-Xaa-Yaa-) repeating sequence of 78 to 81 residues in the N-terminal regions of the constituent A, B and C chains, on the mode of disulphide linkage between the 18 chains of C1q, and on its electron microscopically derived gross structure. It is demonstrated that the interruptions of the repeating sequence about half-way along the length of the collagenous regions (Gly36-Ile37-Arg38-Thr39 in the A chain and Ala36-Ile37-Hy138 in the C chain) do not lead to a disruption of the triple helical conformation but rather to a bend of about 60 degrees in an otherwise continuous triple helix. These features are consistent with a flexibility comparable with that of regular triple helices and with the observed low proteolytic susceptibility of the kink region. The azimuthal orientation of the kink is defined approximately by ArgA38 being located in the cap of the knee. Because of this extra residue between two glycine residues, a bad contact that would arise between the methyl group of AlaC36 and the peptide carbonyl of IleA37 in a straight triple helix is relaxed. The model features also a cluster of hydrophobic contacts between large hydrophobic side-chains in the interaction edges between the six collagen triple helices aligned with their about 10 nm long N-terminal regions in the fibril-like endpiece of C1q. The azimuthal orientations of the triple helices were derived by energy calculations of side-chain interactions previously applied to fibre-forming collagens. Independently, the same orientations and interaction edges were derived from the azimuthal orientation of the kink and the electron microscopically observed orientations of the triple helical arms that emerge from the endpiece, and which carry the C-terminal globular binding domains. The structural model has a number of implications for the assembly of the first component of complement from C1q and the zymogen complex C1r2C1s2 and possible mechanisms of its activation.
通过模型构建和计算机辅助能量优化计算，得到了C1q胶原部分的详细三维模型。所提出的结构基于组成A、B和C链N端区域中78至81个残基的胶原样（-甘氨酸-Xaa-Yaa-）重复序列、C1q的18条链之间的二硫键连接方式以及其电子显微镜下得出的总体结构。结果表明，胶原区域长度约一半处重复序列的中断（A链中的甘氨酸36-异亮氨酸37-精氨酸38-苏氨酸39和C链中的丙氨酸36-异亮氨酸37-羟赖氨酸38）不会导致三螺旋构象的破坏，而是会在原本连续的三螺旋中产生约60度的弯曲。这些特征与规则三螺旋的柔韧性相当，并且与扭结区域观察到的低蛋白水解敏感性一致。扭结的方位取向大致由精氨酸A38位于膝盖帽中来定义。由于两个甘氨酸残基之间存在这个额外的残基，在直的三螺旋中丙氨酸C36的甲基与异亮氨酸A37的肽羰基之间会出现的不良接触得以缓解。该模型的特征还包括在C1q纤维状末端片段中，六个胶原三螺旋与其约10 nm长的N端区域对齐的相互作用边缘处，大的疏水侧链之间存在一簇疏水接触。三螺旋的方位取向是通过先前应用于形成纤维的胶原的侧链相互作用能量计算得出的。独立地，相同的取向和相互作用边缘是从扭结的方位取向以及从末端片段伸出并携带C端球状结合域的三螺旋臂的电子显微镜观察取向中得出的。该结构模型对补体第一成分由C1q和酶原复合物C1r2C1s2组装以及其激活的可能机制有许多启示。
