Source:http://linkedlifedata.com/resource/pubmed/id/21224475
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rdf:type | |
lifeskim:mentions | |
pubmed:issue |
12
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pubmed:dateCreated |
2011-3-25
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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.
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pubmed:grant | |
pubmed:commentsCorrections | |
pubmed:language |
eng
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pubmed:journal | |
pubmed:citationSubset |
AIM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Calcium,
http://linkedlifedata.com/resource/pubmed/chemical/Factor XIII,
http://linkedlifedata.com/resource/pubmed/chemical/Fibrinogen,
http://linkedlifedata.com/resource/pubmed/chemical/Mutant Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Peptide Fragments,
http://linkedlifedata.com/resource/pubmed/chemical/Protein Isoforms,
http://linkedlifedata.com/resource/pubmed/chemical/Recombinant Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/fibrinogen alphaC
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pubmed:status |
MEDLINE
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pubmed:month |
Mar
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pubmed:issn |
1528-0020
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pubmed:author | |
pubmed:issnType |
Electronic
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pubmed:day |
24
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pubmed:volume |
117
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
3460-8
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pubmed:meshHeading |
pubmed-meshheading:21224475-Amino Acid Sequence,
pubmed-meshheading:21224475-Amino Acid Substitution,
pubmed-meshheading:21224475-Calcium,
pubmed-meshheading:21224475-Factor XIII,
pubmed-meshheading:21224475-Fibrinogen,
pubmed-meshheading:21224475-Humans,
pubmed-meshheading:21224475-Molecular Sequence Data,
pubmed-meshheading:21224475-Mutagenesis, Site-Directed,
pubmed-meshheading:21224475-Mutant Proteins,
pubmed-meshheading:21224475-Peptide Fragments,
pubmed-meshheading:21224475-Protein Binding,
pubmed-meshheading:21224475-Protein Interaction Domains and Motifs,
pubmed-meshheading:21224475-Protein Interaction Mapping,
pubmed-meshheading:21224475-Protein Isoforms,
pubmed-meshheading:21224475-Recombinant Proteins,
pubmed-meshheading:21224475-Sequence Homology, Amino Acid
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pubmed:year |
2011
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pubmed:articleTitle |
Interactions between factor XIII and the alphaC region of fibrinogen.
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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.
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pubmed:publicationType |
Journal Article,
In Vitro,
Research Support, Non-U.S. Gov't
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