Modular organization of proteins containing C1q-like globular domain
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- 作者：Kishore ; Uday ; Reid ; Kenneth B.M.
- 关键词：C1q ; Globular head ; Homotrimer ; Modules ; Complement ; ghA ; carboxy-terminal globular region of the C1q A-chain ; ghB ; carboxy-terminal globular region of the C1q B-chain ; ghC ; carboxy-terminal globular region of the C1q C-chain ; IgG ; immunoglobulin G ; IgM
- 刊名：Immunopharmacology
- 出版年：1999
- 出版时间：May, 1999
- 年：1999
- 卷：42
- 期：1-3
- 页码：15-21
- 全文大小：211 K
文摘
The first step in the activation of the classical pathway of complement cascade by immune complexes involves the binding of the six globular heads of C1q to the Fc regions of immunoglobulin G (IgG) or immunoglobulin M (IgM). The globular heads of C1q are located C-terminal to the six triple-helical stalks present in the molecule, each head is considered to be composed of the C-terminal halves (3×135 residues) of one A-, one B- and one C-chain. It is not known if the C-terminal globular regions, present in each of the three types of chains, are independently folded modules (with each chain having distinct binding properties towards immunoglobulins) or whether the different binding functions of C1q are dependent upon a globular structure which relies on contributions from all three chains. Recent reports of recombinant production and characterisation of soluble globular head regions of all the three chains indicate that the globular regions of C1q may adopt a modular organization, i.e., each globular head of C1q may be composed of three, structurally and functionally, independent domains, thus retaining multivalency in the form of a heterotrimer. Modules of the same type as the C1q C-terminal module are also found in a variety of noncomplement proteins that include the C-terminal regions of the human type VIII and type X collagens, precerebellin, the chipmunk hibernation proteins, the human endothelial cell protein, multimerin, the serum protein, Acrp-30 which is secreted from mouse adipocytes, and the sunfish inner-ear specific structural protein. The C1q molecule is the only one of these proteins for which, to date, a function has been ascribed to the module. The existence of a shared structural region between C1q and certain collagens may suggest an evolutionarily common ancestral precursor. Various structural and biochemical data suggest that these modules may be responsible for multimerisation through patches of aromatic residues within them.