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.
Escudero Esparza, Astrid LU ; Kalchishkova, Nikolina LU ; Kurbasic, Emila LU ; Jiang, Wen G and Blom, Anna LU
(2013)
In FASEB Journal
27(12).
p.5083-5093
- Abstract
- 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... (More)
- 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. (Less)
Please use this url to cite or link to this publication:
https://lup.lub.lu.se/record/4005436
- author
- Escudero Esparza, Astrid
LU
; Kalchishkova, Nikolina
LU
; Kurbasic, Emila
LU
; Jiang, Wen G
and Blom, Anna
LU
- organization
- publishing date
- 2013
- type
- Contribution to journal
- publication status
- published
- subject
- in
- FASEB Journal
- volume
- 27
- issue
- 12
- pages
- 5083 - 5093
- publisher
- Wiley
- external identifiers
-
- wos:000329999000040
- pmid:23964079
- scopus:84890479125
- pmid:23964079
- ISSN
- 1530-6860
- DOI
- 10.1096/fj.13-230706
- language
- English
- LU publication?
- yes
- id
- 954981db-e050-4e94-ac8b-1e70f1432f4c (old id 4005436)
- alternative location
- http://www.ncbi.nlm.nih.gov/pubmed/23964079?dopt=Abstract
- date added to LUP
- 2016-04-01 10:11:33
- date last changed
- 2023-08-30 20:12:55
@article{954981db-e050-4e94-ac8b-1e70f1432f4c,
abstract = {{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.}},
author = {{Escudero Esparza, Astrid and Kalchishkova, Nikolina and Kurbasic, Emila and Jiang, Wen G and Blom, Anna}},
issn = {{1530-6860}},
language = {{eng}},
number = {{12}},
pages = {{5083--5093}},
publisher = {{Wiley}},
series = {{FASEB Journal}},
title = {{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.}},
url = {{http://dx.doi.org/10.1096/fj.13-230706}},
doi = {{10.1096/fj.13-230706}},
volume = {{27}},
year = {{2013}},
}