| Research Abstract |
Membrane cofactor protein, MCP,is a complement inhibitor, which prevents autologous complement attack to host cells. In addition, MCP is a receptor of measles virus. Low molecular active fragments of MCP seemed to be useful to prevent the hyper acute ejection of zeno-transplanted organs and measles virus infection. We have investigated the functional domains of MCP essential for the complement regulation and measles virus binding.
i : Functional sites of SCR of MCP
The extra cellular portion of MCP consisted of four tandem repeats of a domain nemed short consensus repeat (SCR). Experiments using biotechnological methods revealed that i ; SCR1 and 2 are essential for measles virus infection, ii ; SCR2 and 3 are essential for the ergulation of the complement activation through the classical pathway, iii ; SCR2,3, and 4 are essential for the regulation of the complement activation through the alternative pathway.
ii : Modulation of MCP functions by serine-threonine rich (ST) regions
The SCR region of MCP was followed by a short sequence rich in Ser/Thr. There are three isoforms of ST region, ST^<ABC>, ST^<BC>, and ST^C are expressed tissue-specifically. The sequence of measles virus infection and the regulatory function to the classical pathway of three ST-isoforms was ST^C>ST^<BC>>ST^<ABC>. On the other hand, the regulatory activity to the alternative pathway was ST^<ABC>>ST^<BC>>ST^C.
iii : Importance of the membrane fraction of MCP for measles virus infection
We designed a GPl-anchored form of MCP,which is devoid of membrane fraction and intracellular domain and binding to cell surface via glycosylated inositol. The GPl-anchored MCP did not mediate measles virus infection, indicating the importance of the membrane fraction of MCP for the internalization of measles virus.
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