MCB
Home Help [Feedback] [For Subscribers] [Archive] [Search] [Contents]
This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrowReprints and Permissions
Right arrow Copyright Information
Right arrow Books from ASM Press
Right arrow MicrobeWorld
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Huang, J.
Right arrow Articles by Kedes, L.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Huang, J.
Right arrow Articles by Kedes, L.

 Previous Article  |  Next Article 

Molecular and Cellular Biology, September 1998, p. 5478-5484, Vol. 18, No. 9
0270-7306/98/$04.00+0
Copyright © 1998, American Society for Microbiology. All rights reserved.

Intramolecular Regulation of MyoD Activation Domain Conformation and Functiondagger

Jing Huang,1 Hal Weintraub,2 and Larry Kedes1,*

Institute for Genetic Medicine and Department of Biochemistry and Molecular Biology, University of Southern California School of Medicine, Los Angeles, California 90033,1 and Howard Hughes Medical Institute, Fred Hutchinson Cancer Research Center, Seattle, Washington 981042

Received 10 November 1997/Returned for modification 15 December 1997/Accepted 8 May 1998

The MyoD family of basic helix-loop-helix (bHLH) proteins is required for myogenic determination and differentiation. The basic region carries the myogenic code and DNA binding specificity, while the N terminus contains a potent transcriptional activation domain. Myogenic activation is abolished when the basic region, bound to a myogenic E box, carries a mutation of Ala-114. It has been proposed that DNA binding of the MyoD basic region leads to recruitment of a recognition factor that unmasks the activation domain. Here we demonstrate that an A114N mutant exhibits an altered conformation in the basic region and that this local conformational difference can lead to a more global change affecting the conformation of the activation domain. This suggests that the deleterious effects of this class of mutations may result directly from defective conformation. Thus, the activation domain is unmasked only upon DNA binding by the correct basic region. Such a coupled conformational relationship may have evolved to restrict myogenic specificity to a small number of bHLH proteins among many with diverse functions yet with DNA binding specificities known to be similar.

* Corresponding author. Mailing address: Institute for Genetic Medicine and Department of Biochemistry and Molecular Biology, University of Southern California School of Medicine, 2250 Alcazar St., Los Angeles, CA 90033. Phone: (323) 442-1145. Fax: (323) 442-2764. E-mail: kedes{at}hsc.usc.edu.

dagger J.H. dedicates this paper to the memory of Man-Hua Wu.

Molecular and Cellular Biology, September 1998, p. 5478-5484, Vol. 18, No. 9
0270-7306/98/$04.00+0
Copyright © 1998, American Society for Microbiology. All rights reserved.


This article has been cited by other articles:



Home Help [Feedback] [For Subscribers] [Archive] [Search] [Contents]
J. Bacteriol. J. Virol. Eukaryot. Cell
Microbiol. Mol. Biol. Rev. Clin. Vaccine Immunol. All ASM Journals

Copyright © 1998 by the American Society for Microbiology. All rights reserved.