HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) Submit a Letter to Editor Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by van de Poel, R. H. L. Articles by Bouma, B. N. Search for Related Content PubMed PubMed Citation Articles by van de Poel, R. H. L. Articles by Bouma, B. N. Social Bookmarking                      What's this?

J Biol Chem, Vol. 274, Issue 21, 15144-15150, May 21, 1999

Interaction between Protein S and Complement C4b-binding Protein (C4BP)
AFFINITY STUDIES USING CHIMERAS CONTAINING C4BP -CHAIN SHORT CONSENSUS REPEATS

From the Thrombosis and Haemostasis Laboratory, Department of Haematology, University Medical Center Utrecht, 3508 GA Utrecht, The Netherlands and the Institute of Biomembranes, Utrecht University, 3584 CH Utrecht, The Netherlands

Human C4b-binding protein (C4BP) is a regulator of the complement system and plays an important role in the regulation of the anticoagulant protein C pathway. C4BP can bind anticoagulant protein S, resulting in a decreased cofactor function of protein S for activated protein C. C4BP is a multimeric protein containing several identical -chains and a single -chain (C4BP), each chain being composed of short consensus repeats (SCRs). Previous studies have localized the protein S binding site to the NH₂-terminal SCR (SCR-1) of C4BP. To further localize the protein S binding site, we constructed chimeras containing C4BP SCR-1, SCR-2, SCR-3, SCR-1+2, SCR-1+3, and SCR-2+3 fused to tissue-type plasminogen activator. Binding assays of protein S with these chimeras indicated that SCR-2 contributes to the interaction of protein S with SCR-1, since the affinity of protein S for SCR-1+2 was up to 5-fold higher compared with SCR-1 and SCR-1+3. Using an assay that measures protein S cofactor activity, we showed that cofactor activity was decreased due to binding to constructs that contain SCR-1. SCR-1+2 inhibited more potently than SCR-1 and SCR-1+3. SCR-3 had no additional effect on SCR-1, and therefore the effect of SCR-2 was specific. In conclusion, -chain SCR-2 contributes to the interaction of C4BP with protein S.

CiteULike

Complore

Connotea

Del.icio.us

Digg

Reddit

Technorati

This article has been cited by other articles:

				L. F. A. Maurissen, M. C. L. G. D. Thomassen, G. A. F. Nicolaes, B. Dahlback, G. Tans, J. Rosing, and T. M. Hackeng Re-evaluation of the role of the protein S-C4b binding protein complex in activated protein C-catalyzed factor Va-inactivation Blood, March 15, 2008; 111(6): 3034 - 3041. [Abstract] [Full Text] [PDF]

				J. H. Webb, A. M. Blom, and B. Dahlback Vitamin K-Dependent Protein S Localizing Complement Regulator C4b-Binding Protein to the Surface of Apoptotic Cells J. Immunol., September 1, 2002; 169(5): 2580 - 2586. [Abstract] [Full Text] [PDF]

				T. K. Giri, S. Linse, P. G. de Frutos, T. Yamazaki, B. O. Villoutreix, and B. Dahlback Structural Requirements of Anticoagulant Protein S for Its Binding to the Complement Regulator C4b-binding Protein J. Biol. Chem., April 19, 2002; 277(17): 15099 - 15106. [Abstract] [Full Text] [PDF]

				J. H. Webb, B. O. Villoutreix, B. Dahlback, and A. M. Blom Localization of a Hydrophobic Binding Site for Anticoagulant Protein S on the beta -Chain of Complement Regulator C4b-binding Protein J. Biol. Chem., February 2, 2001; 276(6): 4330 - 4337. [Abstract] [Full Text] [PDF]