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The novel complement inhibitor human CUB and Sushi multiple domains 1 (CSMD1) protein promotes factor I-mediated degradation of C4b and C3b and inhibits the membrane attack complex assembly.

In English

Författare

  • Astrid Escudero Esparza
  • Nikolina Kalchishkova
  • Emila Kurbasic
  • Wen G Jiang
  • Anna Blom

Summary, in English

CUB and Sushi multiple domains 1 (CSMD1) is a transmembrane protein containing 15 consecutive complement control protein (CCP) domains, which are characteristic for complement inhibitors. We expressed a membrane-bound fragment of human CSMD1 composed of the 15 C-terminal CCP domains and demonstrated that it inhibits deposition of C3b by the classical pathway on the surface of Chinese hamster ovary cells by 70% at 6% serum and of C9 (component of membrane attack complex) by 90% at 1.25% serum. Furthermore, this fragment of CSMD1 served as a cofactor to factor I-mediated degradation of C3b. In all functional assays performed, well-characterized complement inhibitors were used as positive controls, whereas Coxsackie adenovirus receptor, a protein with no effect on complement, was a negative control. Moreover, attenuation of expression in human T47 breast cancer cells that express endogenous CSMD1 significantly increased C3b deposition on these cells by 45% at 8% serum compared with that for the controls. Furthermore, by expressing a soluble 17-21 CCP fragment of CSMD1, we found that CSMD1 inhibits complement by promoting factor I-mediated C4b/C3b degradation and inhibition of MAC assembly at the level of C7. Our results revealed a novel complement inhibitor for the classical and lectin pathways.-Escudero-Esparza, A., Kalchishkova, N., Kurbasic, E., Jiang, W. G., Blom, A. M. The novel complement inhibitor human CUB and Sushi multiple domains 1 (CSMD1) protein promotes factor I-mediated degradation of C4b and C3b and inhibits the membrane attack complex assembly.

Avdelning/ar

Publiceringsår

2013

Språk

Engelska

Sidor

5083-5093

Publikation/Tidskrift/Serie

FASEB Journal

Volym

27

Issue

12

Dokumenttyp

Artikel i tidskrift

Förlag

The Federation of American Societies for Experimental Biology

Ämne

  • Cell and Molecular Biology

Status

Published

Forskningsgrupp

  • Protein Chemistry, Malmö

ISBN/ISSN/Övrigt

  • ISSN: 1530-6860