The Kaposi's sarcoma-associated herpesvirus complement control protein (KCP) binds to heparin and cell surfaces via positively charged amino acids in CCP1-2.
Mark, Linda LU ; Lee, Wen H ; Spiller, O Brad ; Villoutreix, Bruno O and Blom, Anna LU
(2006)
In Molecular Immunology
43(10).
p.1665-1675
- Abstract
- The Kaposi's, sarcoma-associated herpesvirus (KSHV) complement control protein (KCP) inhibits the human complement system, and is similar in structure and function to endogenous complement inhibitors. Other inhibitors such as C4d-binding protein and factor H, as well as the viral homologue vaccinia virus complement control protein are known to bind heparin and, for the two latter, also to glycosaminoglycans at the surface of cells. We report here that KCP also binds to heparin at physiological ionic strength. With help of site directed mutagenesis, positively charged amino acids in the two N-terminal complement control protein (CCP) domains 1-2 were found to be necessary for heparin binding. In silico molecular docking of heparin to KCP... (More)
- The Kaposi's, sarcoma-associated herpesvirus (KSHV) complement control protein (KCP) inhibits the human complement system, and is similar in structure and function to endogenous complement inhibitors. Other inhibitors such as C4d-binding protein and factor H, as well as the viral homologue vaccinia virus complement control protein are known to bind heparin and, for the two latter, also to glycosaminoglycans at the surface of cells. We report here that KCP also binds to heparin at physiological ionic strength. With help of site directed mutagenesis, positively charged amino acids in the two N-terminal complement control protein (CCP) domains 1-2 were found to be necessary for heparin binding. In silico molecular docking of heparin to KCP confirmed the experimental data, and further explored the heparin binding site. enabling us to present a model of the KCP-heparin interaction. Furthermore, the docking analysis also yielded insights of the KCP structure, by indicating that the angle between CCP domains 1-2 during the initial binding of heparin is more extended than in the model we have previously presented. We also found that KCP binds to heparan sulfate and weakly to glycosaminoglycans at the surface of cells. This might indicate that KCP at the Surface of viral particles aids in the primary attachment to the target cells, which is known to involve binding to heparan sulfate. Therefore. the present study contributes to the knowledge of heparin-protein interactions in general its well as to the understanding of the biology of KSHV. (c) 2005 Elsevier Ltd. All rights reserved. (Less)
Please use this url to cite or link to this publication:
https://lup.lub.lu.se/record/150030
- author
- Mark, Linda
LU
; Lee, Wen H
; Spiller, O Brad
; Villoutreix, Bruno O
and Blom, Anna
LU
- organization
- publishing date
- 2006
- type
- Contribution to journal
- publication status
- published
- subject
- in
- Molecular Immunology
- volume
- 43
- issue
- 10
- pages
- 1665 - 1675
- publisher
- Pergamon Press Ltd.
- external identifiers
-
- pmid:16442624
- wos:000236450900018
- scopus:33644537627
- pmid:16442624
- ISSN
- 1872-9142
- DOI
- 10.1016/j.molimm.2005.09.016
- language
- English
- LU publication?
- yes
- id
- 672f2de7-7cd8-4149-b7eb-43a28bc9f5a8 (old id 150030)
- alternative location
- http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=16442624&dopt=Abstract
- date added to LUP
- 2016-04-01 16:17:07
- date last changed
- 2022-01-28 18:39:22
@article{672f2de7-7cd8-4149-b7eb-43a28bc9f5a8,
abstract = {{The Kaposi's, sarcoma-associated herpesvirus (KSHV) complement control protein (KCP) inhibits the human complement system, and is similar in structure and function to endogenous complement inhibitors. Other inhibitors such as C4d-binding protein and factor H, as well as the viral homologue vaccinia virus complement control protein are known to bind heparin and, for the two latter, also to glycosaminoglycans at the surface of cells. We report here that KCP also binds to heparin at physiological ionic strength. With help of site directed mutagenesis, positively charged amino acids in the two N-terminal complement control protein (CCP) domains 1-2 were found to be necessary for heparin binding. In silico molecular docking of heparin to KCP confirmed the experimental data, and further explored the heparin binding site. enabling us to present a model of the KCP-heparin interaction. Furthermore, the docking analysis also yielded insights of the KCP structure, by indicating that the angle between CCP domains 1-2 during the initial binding of heparin is more extended than in the model we have previously presented. We also found that KCP binds to heparan sulfate and weakly to glycosaminoglycans at the surface of cells. This might indicate that KCP at the Surface of viral particles aids in the primary attachment to the target cells, which is known to involve binding to heparan sulfate. Therefore. the present study contributes to the knowledge of heparin-protein interactions in general its well as to the understanding of the biology of KSHV. (c) 2005 Elsevier Ltd. All rights reserved.}},
author = {{Mark, Linda and Lee, Wen H and Spiller, O Brad and Villoutreix, Bruno O and Blom, Anna}},
issn = {{1872-9142}},
language = {{eng}},
number = {{10}},
pages = {{1665--1675}},
publisher = {{Pergamon Press Ltd.}},
series = {{Molecular Immunology}},
title = {{The Kaposi's sarcoma-associated herpesvirus complement control protein (KCP) binds to heparin and cell surfaces via positively charged amino acids in CCP1-2.}},
url = {{https://lup.lub.lu.se/search/files/4626085/625251.pdf}},
doi = {{10.1016/j.molimm.2005.09.016}},
volume = {{43}},
year = {{2006}},
}