Linked Life Data

21806028

Source:http://linkedlifedata.com/resource/pubmed/id/21806028

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
37
pubmed:dateCreated
2011-9-13
pubmed:abstractText
Our previous studies revealed that in fibrinogen the ?C-domains are not reactive with their ligands, suggesting that their binding sites are cryptic and become exposed upon its conversion to fibrin, in which these domains form ?C polymers. On the basis of this finding, we hypothesized that polymerization of the ?C-domains in fibrin results in the exposure of their binding sites and that these domains adopt the physiologically active conformation only in ?C-domain polymers. To test this hypothesis, we prepared a recombinant ?C region (residues A?221-610) including the ?C-domain (A?392-610), demonstrated that it forms soluble oligomers in a concentration-dependent and reversible manner, and stabilized such oligomers by covalently cross-linking them with factor XIIIa. Cross-linked A?221-610 oligomers were stable in solution and appeared as ordered linear, branching filaments when analyzed by electron microscopy. Spectral studies revealed that the ?C-domains in such oligomers were folded into compact structures of high thermal stability with a significant amount of ?-sheets. These findings indicate that cross-linked A?221-610 oligomers are highly ordered and mimic the structure of fibrin ?C polymers. The oligomers also exhibited functional properties of polymeric fibrin because, in contrast to the monomeric ?C-domain, they bound tPA and plasminogen and stimulated activation of the latter by the former. Altogether, the results obtained with cross-linked A?221-610 oligomers clarify the structure of the ?C-domains in fibrin ?C polymers and confirm our hypothesis that their binding sites are exposed upon polymerization. Such oligomers represent a stable, soluble model of fibrin ?C polymers that can be used for further structure-function studies of fibrin ?C-domains.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Sep
pubmed:issn
1520-4995
pubmed:author
pubmed:copyrightInfo
© 2011 American Chemical Society
pubmed:issnType
Electronic
pubmed:day
20
pubmed:volume
50
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
8028-37
pubmed:meshHeading
pubmed:year
2011
pubmed:articleTitle
Structure, stability, and interaction of fibrin ?C-domain polymers.
pubmed:affiliation
Center for Vascular and Inflammatory Diseases and Department of Biochemistry and Molecular Biology, University of Maryland School of Medicine, Baltimore, Maryland 21201-1138, USA.
pubmed:publicationType
Journal Article, Comparative Study, Research Support, N.I.H., Extramural