Linked Life Data

10744423

Source:http://linkedlifedata.com/resource/pubmed/id/10744423

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
5-6
pubmed:dateCreated
2000-3-28
pubmed:abstractText
C4b-binding protein (C4BP) regulates the complement system and the anticoagulant activity of protein S. Protein S can bind to C4BP, resulting in a decreased cofactor activity of protein S for anticoagulant activated protein C. C4BP contains several identical a-chains and a single 3-chain. Each chain contains Short Consensus Repeats (SCRs). By making chimeras of 13-chain SCRs fused to tissue-type plasminogen activator (tPA chimeras), we found that 13-chain SCR-2 contributed to the interaction of 13-chain SCR-1 with protein S (van de Poel RHL, Meijers JCM, Bouma BN. J Biol Chem 274:15144-15150, 1999). Chimeras containing C4BP a-chains with SCR-1, SCR-l +2 or SCR-l +2+3 replaced by their 13-chain counterpart had affinities for protein S similar to C4BP (Hardig Y, Dahlb¿ck B. J Biol Chem 271:20861-20867, 1996). This was not in agreement with the finding that Beta-chain SCR-2 contributed to the interaction and could be explained by the possibility that alpha-chain SCR-2 in the alpha-chain chimeras contributed comparable with Beta-chain SCR-2 in the tPA chimeras. To investigate this we constructed a tPA chimera containing Beta-chain SCR-1 and alpha-chain SCR-2 (Beta1alpha2). Binding studies showed that Beta1alpha2 had a lower affinity compared with SCR-1 +2, indicating that alpha-chain SCR-2 did not contribute to the interaction. The difference with the alpha-chain chimeras may be explained by the fact that the alpha-chain chimeras were linked by their C-terminal cysteines, resulting in multiple binding sites in a single molecule. Thereby, the effect of a lower affinity of each alpha-chain chimera may have been masked. The studies performed here help to clarify the apparent inconsistencies in two previous reports about the contribution of the SCR-2 domain in C4BP to protein S binding. In conclusion, Beta-chain SCR-2 specifically contributes to the interaction of SCR-1 with protein S.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:issn
1079-9796
pubmed:author
pubmed:issnType
Print
pubmed:volume
25
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
279-86
pubmed:dateRevised
2007-8-8
pubmed:meshHeading
pubmed-meshheading:10744423-Animals, pubmed-meshheading:10744423-Anticoagulants, pubmed-meshheading:10744423-Binding, Competitive, pubmed-meshheading:10744423-Blood Coagulation, pubmed-meshheading:10744423-Cell Culture Techniques, pubmed-meshheading:10744423-Complement Inactivator Proteins, pubmed-meshheading:10744423-Consensus Sequence, pubmed-meshheading:10744423-Cricetinae, pubmed-meshheading:10744423-Glycoproteins, pubmed-meshheading:10744423-Humans, pubmed-meshheading:10744423-Protein Binding, pubmed-meshheading:10744423-Protein S, pubmed-meshheading:10744423-Receptors, Complement, pubmed-meshheading:10744423-Recombinant Fusion Proteins, pubmed-meshheading:10744423-Repetitive Sequences, Amino Acid, pubmed-meshheading:10744423-Tissue Plasminogen Activator, pubmed-meshheading:10744423-Transfection
pubmed:articleTitle
C4b-binding protein (C4BP) beta-chain Short Consensus Repeat-2 specifically contributes to the interaction of C4BP with protein S.
pubmed:affiliation
Thrombosis and Haemostasis Laboratory, Department of Haematology, University Medical Center Utrecht, 3508 GA Utrecht, The Netherlands.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't