Linked Life Data

14661957

Source:http://linkedlifedata.com/resource/pubmed/id/14661957

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
49
pubmed:dateCreated
2003-12-9
pubmed:abstractText
We have utilized 2D [(1)H,(15)N]HSQC NMR spectroscopy to elucidate the binding of three segments of cTnI in native, phosphorylated, and mutated states to cTnC. The near N-terminal region (cRp; residues 34-71) contains the protein kinase C (PKC) phosphorylation sites S41 and S43, the inhibitory region (cIp; residues 128-147) contains another PKC site T142 and a familial hypertrophic cardiomyopathy (FHC) mutation R144G, and the switch region (cSp; residues 147-163) contains the novel p21-activated kinase (PAK) site S149 and another FHC mutation R161W. While S41/S43 phosphorylation of cRp had minimal disruption in the interaction of cRp and cTnC.3Ca(2+), T142 phosphorylation reduced the affinity of cIp for cCTnC.2Ca(2+) by approximately 14-fold and S149 phosphorylation reduced the affinity of cSp for cNTnC.Ca(2+) by approximately 10-fold. The mutation R144G caused an approximately 6-fold affinity decrease of cIp for cCTnC.2Ca(2+) and mutation R161W destabilized the interaction of cSp and cNTnC.Ca(2+) by approximately 1.4-fold. When cIp was both T142 phosphorylated and R144G mutated, its affinity for cCTnC.2Ca(2+) was reduced approximately 19-fold, and when cSp was both S149 phosphorylated and R161W mutated, its affinity for cNTnC.Ca(2+) was reduced approximately 4-fold. Thus, while the FHC mutation R144G enhances the effect of T142 phosphorylation on the interaction of cIp and cCTnC.2Ca(2+), the FHC mutation R161W suppresses the effect of S149 phosphorylation on the interaction of cSp and cNTnC.Ca(2+), demonstrating linkages between the FHC mutation and phosphorylation of cTnI. The observed alterations corroborate well with structural data. These results suggest that while the modifications in the cRp region have minimal influence, those in the key functional cIp-cSp region have a pronounced effect on the interaction of cTnI and cTnC, which may correlate with the altered myofilament function and cardiac muscle contraction under pathophysiological conditions.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Dec
pubmed:issn
0006-2960
pubmed:author
pubmed:issnType
Print
pubmed:day
16
pubmed:volume
42
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
14460-8
pubmed:dateRevised
2006-11-15
pubmed:meshHeading
pubmed-meshheading:14661957-Amino Acid Sequence, pubmed-meshheading:14661957-Arginine, pubmed-meshheading:14661957-Calcium, pubmed-meshheading:14661957-Cardiomyopathy, Hypertrophic, Familial, pubmed-meshheading:14661957-Glycine, pubmed-meshheading:14661957-Humans, pubmed-meshheading:14661957-Molecular Sequence Data, pubmed-meshheading:14661957-Mutagenesis, Site-Directed, pubmed-meshheading:14661957-Myocardium, pubmed-meshheading:14661957-Nuclear Magnetic Resonance, Biomolecular, pubmed-meshheading:14661957-Peptide Fragments, pubmed-meshheading:14661957-Phosphorylation, pubmed-meshheading:14661957-Protein Binding, pubmed-meshheading:14661957-Protein Structure, Tertiary, pubmed-meshheading:14661957-Recombinant Proteins, pubmed-meshheading:14661957-Serine, pubmed-meshheading:14661957-Threonine, pubmed-meshheading:14661957-Troponin C, pubmed-meshheading:14661957-Troponin I, pubmed-meshheading:14661957-Tryptophan
pubmed:year
2003
pubmed:articleTitle
Phosphorylation and mutation of human cardiac troponin I deferentially destabilize the interaction of the functional regions of troponin I with troponin C.
pubmed:affiliation
CIHR Group in Protein Structure and Function, Department of Biochemistry, University of Alberta, Edmonton, Alberta, Canada T6G 2H7.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't