Linked Life Data

16705085

Source:http://linkedlifedata.com/resource/pubmed/id/16705085

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
6
pubmed:dateCreated
2006-9-7
pubmed:abstractText
To examine the role of fibrinogen gamma-chain residue 387Ile in the assembly and secretion of this multichain protein, we synthesized a series of variants with substitution at gamma387 by Arg, Leu, Met, Ala, or Asp. Only the variant gamma387Asp showed impaired synthesis in the cells and very low secretion into the medium. In addition, we performed thrombin-catalyzed fibrin polymerization and factor (F) XIIIa-catalyzed cross-linking of the gamma-chain for 4 variants. The degree of lateral aggregation of protofibrils into fibrin fibers was slightly reduced for gamma387Arg and Ala, and moderately reduced for gamma387Leu and Met. Although the FXIIIa-catalyzed cross-linking for all of the variants was slower than that for gamma387Ile, that of gamma387Arg was much more markedly impaired than that of the others. In summary, our studies demonstrated that the specific residue at gamma387 or the conformation of gamma388-411 residues, but not the length of the gammaC tail, is critical for fibrinogen assembly and subsequent secretion. Moreover, this residue or the conformation is also important for not only the lateral aggregation of fibrin polymers but also the FXIIIa-catalyzed cross-linking of the gamma-chain. Interestingly, our results clearly indicate that the conformations critical for these 2 functions are different from each other.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
AIM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Sep
pubmed:issn
0006-4971
pubmed:author
pubmed:issnType
Print
pubmed:day
15
pubmed:volume
108
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1887-94
pubmed:dateRevised
2008-11-21
pubmed:meshHeading
pubmed-meshheading:16705085-Amino Acid Substitution, pubmed-meshheading:16705085-Animals, pubmed-meshheading:16705085-Base Sequence, pubmed-meshheading:16705085-CHO Cells, pubmed-meshheading:16705085-Cricetinae, pubmed-meshheading:16705085-DNA, Complementary, pubmed-meshheading:16705085-Dimerization, pubmed-meshheading:16705085-Factor XIIIa, pubmed-meshheading:16705085-Fibrinogen, pubmed-meshheading:16705085-Fibrinogens, Abnormal, pubmed-meshheading:16705085-Genetic Variation, pubmed-meshheading:16705085-Humans, pubmed-meshheading:16705085-Models, Molecular, pubmed-meshheading:16705085-Multiprotein Complexes, pubmed-meshheading:16705085-Mutagenesis, Site-Directed, pubmed-meshheading:16705085-Protein Structure, Quaternary, pubmed-meshheading:16705085-Protein Structure, Tertiary, pubmed-meshheading:16705085-Recombinant Proteins
pubmed:year
2006
pubmed:articleTitle
Analysis of fibrinogen variants at gamma387Ile shows that the side chain of gamma387 and the tertiary structure of the gammaC-terminal tail are important not only for assembly and secretion of fibrinogen but also for lateral aggregation of protofibrils and XIIIa-catalyzed gamma-gamma dimer formation.
pubmed:affiliation
Laboratory of Clinical Chemistry, Department of Biomedical Laboratory Sciences, School of Health Sciences, Shinshu University, 3-1-1 Asahi, Matsumoto 390-8621, Japan.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't