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Interaction of levosimendan with cadiac troponin C in the presence of cardiac troponin I peptides.

In English

Författare

  • T Sorsa
  • P Pollesello
  • P Permi
  • Torbjörn Drakenberg
  • I Kilpeläinen

Summary, in English

The interaction between troponin C (TnC) and troponin I (TnI) is essential for the regulation of muscle contraction. There are several binding sites for TnI on TnC that are differentially occupied depending on the phase of the contraction/relaxation cycle. TnI and TnC interact in an antiparallel fashion with each other. The C-domain of cTnC and the N-domain region of cTnI(residues 33–70) always interact under physiological conditions, whereas the interaction between regulatory regions of TnC and TnI (residues 128–166) is calcium dependent. Previously, it has been shown that levosimendan, a calcium sensitizer used as a treatment for acute heart failure, can interact with both domains of isolated cTnC. To understand which interaction is relevant for the mechanism of calcium sensitization, we used a more complete troponin model obtained by complexing cTnI32–79 and cTnI128–180 with calcium-saturated cTnCCS. The cTnI peptides bound to cTnCCS to form a 1:1:1 complex. The interaction of levosimendan with this complex was followed by 1H–15N heteronuclear correlation spectroscopy. It was clear that based on chemical shift changes, cTnI32–79 blocked the levosimendan interaction sites on the C-domain, whereas cTnI128–180 did not compete with levosimendan for the binding site on the N-domain. Hence, the effective binding site of levosimendan on cTnC resulting in the calcium-sensitizing effect is located in the regulatory domain (N-domain).

Avdelning/ar

Publiceringsår

2003

Språk

Engelska

Sidor

1055-1061

Publikation/Tidskrift/Serie

Journal of Molecular and Cellular Cardiology

Volym

35

Issue

9

Dokumenttyp

Artikel i tidskrift

Förlag

Elsevier

Ämne

  • Cardiac and Cardiovascular Systems

Status

Published

ISBN/ISSN/Övrigt

  • ISSN: 1095-8584