| http://purl.uniprot.org/citations/27429059 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/27429059 | http://www.w3.org/2000/01/rdf-schema#comment | "Troponin T (TnT) is the tropomyosin (Tm)-binding and thin filament-anchoring subunit of troponin and plays a central role in striated muscle contraction. A nonsense mutation in exon 11 of the TNNT1 gene encoding slow skeletal muscle troponin T (ssTnT) truncating the polypeptide chain at Glu(180) causes a lethal recessive nemaline myopathy (NM) in the Amish (ANM). More TNNT1 NM mutations have been reported recently with similar recessive phenotypes. A nonsense mutation in exon 9 causes truncation at Ser(108), and a splicing site mutation causes truncation at Leu(203). Another splicing site mutation causes an internal deletion of the 39 exon 8-encoded amino acids. We engineered and characterized these ssTnT mutants to demonstrate that the Ser(108) truncation exhibits a Tm binding affinity lower than that of the ANM Glu(180) truncation, indicating a partial loss of Tm-binding site 1. Despite the presence of Tm-binding sites 1 and 2, ssTnT truncated at Leu(203) binds Tm with decreased affinity, consistent with its recessive NM phenotype and the requirement of troponin complex formation for high-affinity binding of TnT to Tm. The exon 8-deleted ssTnT has a partial loss of Tm-binding site 1 but retains high-affinity Tm-binding site 2. However, exon 8-deleted ssTnT exhibits a dramatically diminished Tm binding affinity, indicating a long-range conformational effect of this middle region deletion. Predicted from the TnT structure-function relationship, removal of the N-terminal variable region partially rescued this negative impact. These novel findings lay a foundation for understanding the pathogenesis of TNNT1 myopathies and provide insights into the development of targeted treatment."xsd:string |
| http://purl.uniprot.org/citations/27429059 | http://purl.org/dc/terms/identifier | "doi:10.1021/acs.biochem.6b00577"xsd:string |
| http://purl.uniprot.org/citations/27429059 | http://purl.uniprot.org/core/author | "Hossain M.M."xsd:string |
| http://purl.uniprot.org/citations/27429059 | http://purl.uniprot.org/core/author | "Jin J.P."xsd:string |
| http://purl.uniprot.org/citations/27429059 | http://purl.uniprot.org/core/author | "Amarasinghe C."xsd:string |
| http://purl.uniprot.org/citations/27429059 | http://purl.uniprot.org/core/date | "2016"xsd:gYear |
| http://purl.uniprot.org/citations/27429059 | http://purl.uniprot.org/core/name | "Biochemistry"xsd:string |
| http://purl.uniprot.org/citations/27429059 | http://purl.uniprot.org/core/pages | "4560-4567"xsd:string |
| http://purl.uniprot.org/citations/27429059 | http://purl.uniprot.org/core/title | "Functional Basis of Three New Recessive Mutations of Slow Skeletal Muscle Troponin T Found in Non-Amish TNNT1 Nemaline Myopathies."xsd:string |
| http://purl.uniprot.org/citations/27429059 | http://purl.uniprot.org/core/volume | "55"xsd:string |
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