Departments of Medicine, Stony Brook University, Stony Brook, NY, United States.
Biosciences, College of Health and Life Sciences, Brunel University London, Uxbridge, United Kingdom.
Front Immunol. 2018 Feb 5;9:162. doi: 10.3389/fimmu.2018.00162. eCollection 2018.
The immunopathological functions associated with human C1q are still growing in terms of novelty, diversity, and pathologic relevance. It is, therefore, not surprising that C1q is being recognized as an important molecular bridge between innate and adaptive immunity. The secret of this functional diversity, in turn, resides in the elegant but complex structure of the C1q molecule, which is assembled from three distinct gene products: A, B, and C, each of which has evolved from a separate and unique ancestral gene template. The C1q molecule is made up of 6A, 6B, and 6C polypeptide chains, which are held together through strong covalent and non-covalent bonds to form the 18-chain, bouquet-of-flower-like protein that we know today. The assembled C1q protein displays at least two distinct structural and functional regions: the collagen-like region (cC1q) and the globular head region (gC1q), each being capable of driving a diverse range of ligand- or receptor-mediated biological functions. What is most intriguing, however, is the observation that most of the functions appear to be predominantly driven by the A-chain of the molecule, which begs the question: what are the evolutionary modifications or rearrangements that singularly shaped the primordial A-chain gene to become a pluripotent and versatile component of the intact C1q molecule? Here, we revisit and discuss some of the known unique structural and functional features of the A-chain, which may have contributed to its versatility.
与人类 C1q 相关的免疫病理学功能在新颖性、多样性和病理学相关性方面仍在不断发展。因此，C1q 被认为是先天免疫和适应性免疫之间的重要分子桥梁，这并不奇怪。这种功能多样性的秘密，反过来又存在于 C1q 分子优雅而复杂的结构中，该分子由三个不同的基因产物组成：A、B 和 C，每个产物都从一个单独的、独特的祖先基因模板进化而来。C1q 分子由 6A、6B 和 6C 多肽链组成，通过强共价和非共价键结合在一起，形成我们今天所知的 18 链、花束状的蛋白质。组装好的 C1q 蛋白显示出至少两个不同的结构和功能区域：胶原样区域（cC1q）和球形头部区域（gC1q），每个区域都能够驱动多种配体或受体介导的生物学功能。然而，最有趣的是观察到大多数功能似乎主要由分子的 A 链驱动，这就提出了一个问题：是什么样的进化修饰或重排使原始的 A 链基因成为完整的 C1q 分子中多能和多功能的组成部分？在这里，我们回顾并讨论了 A 链的一些已知独特的结构和功能特征，这些特征可能有助于其多功能性。
