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Interdomain orientation of cardiac Troponin C characterized by paramagnetic relaxation enhancement NMR reveals a compact state

journal contribution
posted on 2023-05-17, 13:23 authored by Cordina, NM, Liew, CK, David GellDavid Gell, Fajer, PG, Mackay, JP, Brown, LJ
Cardiac troponin C (cTnC) is the calcium binding subunit of the troponin complex that triggers the thin filament response to calcium influx into the sarcomere. cTnC consists of two globular EF-hand domains (termed the N- and C-domains) connected by a flexible linker. While the conformation of each domain of cTnC has been thoroughly characterized through NMR studies involving either the isolated N-domain (N-cTnC) or C-domain (C-cTnC), little attention has been paid to the range of interdomain orientations possible in full-length cTnC that arises as a consequence of the flexibility of the domain linker. Flexibility in the domain linker of cTnC is essential for effective regulatory function of troponin. We have therefore utilized paramagnetic relaxation enhancement (PRE) NMR to assess the interdomain orientation of cTnC. Ensemble fitting of our interdomain PRE measurements reveals that isolated cTnC has considerable interdomain flexibility and preferentially adopts a bent conformation in solution, with a defined range of relative domain orientations.

History

Publication title

Protein Science

Volume

21

Issue

9

Pagination

1376-1387

ISSN

1469-896X

Department/School

Menzies Institute for Medical Research

Publisher

Wiley-Blackwell Publishing, Inc.

Place of publication

United States

Rights statement

Copyright 2012 The Protein Society

Repository Status

  • Restricted

Socio-economic Objectives

Clinical health not elsewhere classified

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