Change search
ReferencesLink to record
Permanent link

Direct link
A novel type of calmodulin interaction in the inhibition of basic helix-loop-helix transcription factors.
Umeå University, Faculty of Medicine, Molecular Biology (Faculty of Medicine).
Umeå University, Faculty of Medicine, Molecular Biology (Faculty of Medicine).
Umeå University, Faculty of Medicine, Molecular Biology (Faculty of Medicine).
2000 (English)In: Biochemistry, ISSN 0006-2960, E-ISSN 1520-4995, Vol. 39, no 15, 4366-4374 p.Article in journal (Refereed) Published
Abstract [en]

Calmodulin is the predominant intracellular receptor for Ca(2+) signals, mediating the regulation of numerous cellular processes. Previous studies have shown that calcium-loaded calmodulin can bind to and inhibit the activity of certain basic helix-loop-helix (bHLH) transcription factors. The basic sequence within the bHLH domain is the primary target for calmodulin binding, and sequences modulating the calmodulin interaction reside directly N-terminal to the basic sequence. Here we show that the interaction of calmodulin with bHLH proteins is of a novel type, displaying characteristics very different from those of previously characterized calmodulin-target complexes. We show that calmodulin interacts much stronger with a dimeric basic sequence than with the monomeric form. The calmodulin-bHLH protein complex contains equimolar amounts of calmodulin and bHLH chains. The interaction is unusual in being to a large extent polar in nature, and it is highly resistant to tested calmodulin inhibitors. Both the N-terminal and C-terminal domains of calmodulin can independently bind to and inhibit the DNA binding of bHLH proteins. The C-terminal domain preferentially binds to the basic sequence, whereas the N-terminal domain is essential for the effect of the modulatory sequence. We propose a model for the calmodulin-bHLH complex where two calmodulin molecules interact with one bHLH dimer, with one domain of calmodulin preferentially binding to the basic sequence of bHLH proteins and the other domain interacting with the modulatory sequence.

Place, publisher, year, edition, pages
2000. Vol. 39, no 15, 4366-4374 p.
National Category
Medical and Health Sciences
URN: urn:nbn:se:umu:diva-33072DOI: 10.1021/bi992533uPubMedID: 10757985OAI: diva2:309940
Available from: 2010-04-09 Created: 2010-04-09 Last updated: 2010-04-09Bibliographically approved

Open Access in DiVA

No full text

Other links

Publisher's full textPubMed

Search in DiVA

By author/editor
Onions, JacquelineHermann, StefanGrundström, Thomas
By organisation
Molecular Biology (Faculty of Medicine)
In the same journal
Medical and Health Sciences

Search outside of DiVA

GoogleGoogle Scholar
The number of downloads is the sum of all downloads of full texts. It may include eg previous versions that are now no longer available

Altmetric score

Total: 46 hits
ReferencesLink to record
Permanent link

Direct link