Calcium-induced tripartite binding of intrinsically disordered calpastatin to its cognate enzyme, calpain.

TitleCalcium-induced tripartite binding of intrinsically disordered calpastatin to its cognate enzyme, calpain.
Publication TypeJournal Article
Year of Publication2008
AuthorsKiss, R., Z. Bozoky, D. Kovacs, G. Róna, P. Friedrich, P. Dvortsák, R. Weisemann, R. Weisemann, P. Tompa, and A. Perczel
JournalFEBS Lett
Volume582
Issue15
Pagination2149-54
Date Published2008 Jun 25
ISSN0014-5793
KeywordsCalcium, Calcium-Binding Proteins, Calpain, Humans, Nuclear Magnetic Resonance, Biomolecular, Protein Conformation
Abstract

The activity of calpain is controlled by the free intracellular calcium level and by the protein's intrinsically disordered endogenous inhibitor, calpastatin, mediated by short conserved segments: subdomains A-C. The exact binding mode of calpastatin to the enzyme has until now been unclear. Our NMR data of the 141 amino acid long inhibitor, with and without calcium and calpain, have revealed structural changes and a tripartite binding mode, in which the disordered inhibitor wraps around, and contacts, the enzyme at three points, facilitated by flexible linkers. This unprecedented binding mode permits a unique combination of specificity, speed and binding strength in regulation.

DOI10.1016/j.febslet.2008.05.032
Alternate JournalFEBS Lett.
PubMed ID18519038
Grant ListISRF067595 / / Wellcome Trust / United Kingdom