Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
12
pubmed:dateCreated
2011-3-25
pubmed:abstractText
Fibrinogen ?C residues 242-424 have been shown to have a major regulatory role in the activation of factor XIII-A(2)B(2) (FXIII-A(2)B(2)); however, the interactions underpinning this enhancing effect have not been determined. Here, we have characterized the binding of recombinant (r)FXIII-A subunit and FXIII-A(2)B(2) with fibrin(ogen) and fibrin ?C residues 233-425. Using recombinant truncations of the fibrin ?C region 233-425 and surface plasmon resonance, we found that activated rFXIII-A bound ?C 233-425 (K(d) of 2.35 ± 0.09 ?M) which was further localized to ?C 389-403. Site-directed mutagenesis of this region highlighted Glu396 as a key residue for binding of activated rFXIII-A. The interaction was specific for activated rFXIII-A and depended on the calcium-induced conformational change known to occur in rFXIII-A during activation. Furthermore, nonactivated FXIII-A(2)B(2), thrombin-cleaved FXIII-A(2)B(2), and activated FXIII-A(2)B(2) each bound fibrin(ogen) and specifically ?C region 371-425 with high affinity (K(d) < 35 nM and K(d) < 31 nM, respectively), showing for the first time the potential involvement of the ?C region in binding to FXIII-A(2)B(2). These results suggest that in addition to fibrinogen ?' chain binding, the fibrin ?C region also provides a platform for the binding of FXIII-A(2)B(2) and FXIII-A subunit.
pubmed:grant
pubmed:commentsCorrections
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
AIM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Mar
pubmed:issn
1528-0020
pubmed:author
pubmed:issnType
Electronic
pubmed:day
24
pubmed:volume
117
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
3460-8
pubmed:meshHeading
pubmed:year
2011
pubmed:articleTitle
Interactions between factor XIII and the alphaC region of fibrinogen.
pubmed:affiliation
Division of Cardiovascular and Diabetes Research, Leeds Institute for Genetics Health and Therapeutics, Faculty of Medicine and Health, University of Leeds, Leeds, United Kingdom.
pubmed:publicationType
Journal Article, In Vitro, Research Support, Non-U.S. Gov't