Structure, distribution, classification, and function of C1q protein family: a review

Abstract

The C1q protein family consists of many proteins containing a Clq domain, which exists widely within organisms from bacteria to mammals. The domain organization of these proteins mainly includes a leading signal peptide, a collagen-like region, and a globular Clq domain. According to their structural characteristics, the C1q protein family can be divided into three subgroups: C1q, C1q-like and ghC1q. C1q, as the first subcomponent of classical pathway in the complement system, has the ability to bind immune complexes and triggers activation of the classical complement pathway. In addition, it can be a pattern recognition receptor with the unique ability to sense an amazing variety of ligands. C1q-like protein contains a collagen-like region and a globular Clq domain which is similar to Clq molecule. It involves in leech central nervous system repair. However, in vertebrates, its function converts from a lectin to an immunoglobulin binding molecule and it involves in the activation of complement system. The structure of ghC1q protein is composed of a globular Clq domain and a short N-terminal sequence. This protein contains secreted globular head C1q proteins and cellular globular head C1q proteins. The sghClq protein plays an important role in the innate immune system of invertebrates. The sghC1q proteins that belong to vertebrates may serve as a new class of transneuronal regulators of synapse development and synaptic plasticity in various brain regions. The earliest cghC1q gene can be traced back to bacteria of the genus Bacillus. Its stereotypical gC1q jelly roll topology substantiates that the gC1q domain has an ancient evolutionary history and a highly conserved structure. This review focuses on the structure, distribution, classification, and function of C1q family proteins, providing valuable clues for the future research in this field.