Structure and proteolytic susceptibility of the inhibitory C-terminal tail of cardiac troponin I.


Journal

Biochimica et biophysica acta. General subjects
ISSN: 1872-8006
Titre abrégé: Biochim Biophys Acta Gen Subj
Pays: Netherlands
ID NLM: 101731726

Informations de publication

Date de publication:
04 2019
Historique:
received: 14 09 2018
revised: 22 11 2018
accepted: 14 01 2019
pubmed: 20 1 2019
medline: 4 12 2019
entrez: 20 1 2019
Statut: ppublish

Résumé

Cardiac troponin I (cTnI) has two flexible tails that control the cardiac cycle. The C-terminal tail, cTnI Soluble fragments of cTnI containing its N- and C-terminal tails, cTnI cTnI Both N-terminal and C-terminal tails of cTnI are susceptible to cleavage by MMP-2 and calpain-2. Binding to cTnC or actin confers some protection to proteolysis, which can be understood in terms of their interactions as probed by NMR studies. cTnI is an important marker of intracellular proteolysis in cardiomyocytes, given its many protease-specific cut sites, high natural abundance, indispensable functional role, and clinical use as gold standard biomarker of myocardial injury.

Sections du résumé

BACKGROUND
Cardiac troponin I (cTnI) has two flexible tails that control the cardiac cycle. The C-terminal tail, cTnI
METHODS
Soluble fragments of cTnI containing its N- and C-terminal tails, cTnI
RESULTS
cTnI
CONCLUSIONS
Both N-terminal and C-terminal tails of cTnI are susceptible to cleavage by MMP-2 and calpain-2. Binding to cTnC or actin confers some protection to proteolysis, which can be understood in terms of their interactions as probed by NMR studies.
GENERAL SIGNIFICANCE
cTnI is an important marker of intracellular proteolysis in cardiomyocytes, given its many protease-specific cut sites, high natural abundance, indispensable functional role, and clinical use as gold standard biomarker of myocardial injury.

Identifiants

pubmed: 30659884
pii: S0304-4165(19)30014-5
doi: 10.1016/j.bbagen.2019.01.008
pii:
doi:

Substances chimiques

Actins 0
Recombinant Proteins 0
Troponin I 0
Calpain EC 3.4.22.-
CAPN2 protein, human EC 3.4.22.53
Matrix Metalloproteinase 2 EC 3.4.24.24

Types de publication

Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

661-671

Subventions

Organisme : CIHR
Pays : Canada

Informations de copyright

Copyright © 2019 Elsevier B.V. All rights reserved.

Auteurs

Zabed Mahmud (Z)

Department of Biochemistry, University of Alberta, Edmonton, AB T6G 2R3, Canada.

Somaya Zahran (S)

Department of Medicine, University of Alberta, Edmonton, AB T6G 2R3, Canada.

Philip B Liu (PB)

Department of Biochemistry, University of Alberta, Edmonton, AB T6G 2R3, Canada.

Bela Reiz (B)

Department of Chemistry, University of Alberta, Edmonton, AB T6G 2G2, Canada.

Brandon Y H Chan (BYH)

Department of Pediatrics, University of Alberta, Edmonton, AB T6G 1C9, Canada; Department of Pharmacology, University of Alberta, Edmonton, AB T6G 2H7, Canada.

Andrej Roczkowsky (A)

Department of Pediatrics, University of Alberta, Edmonton, AB T6G 1C9, Canada; Department of Pharmacology, University of Alberta, Edmonton, AB T6G 2H7, Canada.

Christian-Scott E McCartney (CE)

Department of Biomedical and Molecular Sciences, Queen's University, Kingston, ON K7L 3N6, Canada.

Peter L Davies (PL)

Department of Biomedical and Molecular Sciences, Queen's University, Kingston, ON K7L 3N6, Canada.

Liang Li (L)

Department of Chemistry, University of Alberta, Edmonton, AB T6G 2G2, Canada.

Richard Schulz (R)

Department of Pediatrics, University of Alberta, Edmonton, AB T6G 1C9, Canada; Department of Pharmacology, University of Alberta, Edmonton, AB T6G 2H7, Canada.

Peter M Hwang (PM)

Department of Biochemistry, University of Alberta, Edmonton, AB T6G 2R3, Canada; Department of Medicine, University of Alberta, Edmonton, AB T6G 2R3, Canada. Electronic address: phwang1@ualberta.ca.

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Classifications MeSH