Skip Navigation

This Article
Right arrow Full Text Freely available
Right arrow Print PDF (540K) Freely available
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in ISI Web of Science
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Add to My Personal Archive
Right arrow Download to citation manager
Right arrow Search for citing articles in:
ISI Web of Science (20)
Right arrowRequest Permissions
Right arrow Commercial Re-use Guidelines
for Open Access NAR Content
Google Scholar
Right arrow Articles by Klass, J.
Right arrow Articles by Churchill, M. E. A.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Klass, J.
Right arrow Articles by Churchill, M. E. A.
Social Bookmarking
Add to CiteULike   Add to Connotea   Add to Del.icio.us  
What's this?

Nucleic Acids Research, 2003, Vol. 31, No. 11 2852-2864
© 2003 Oxford University Press

The role of intercalating residues in chromosomal high-mobility-group protein DNA binding, bending and specificity

Janet Klass1, Frank V. Murphy IV1,2, Susan Fouts1, Melissa Serenil1, Anita Changela2, Jessica Siple2 and Mair E. A. Churchill1

1 Department of Pharmacology, The University of Colorado Health Sciences Center, 4200 East Ninth Avenue, Denver, CO 80262, USA and 2 The Department of Biochemistry, University of Illinois at Urbana-Champaign, 600 South Matthews Avenue, Urbana, IL 61801, USA

*To whom correspondence should be addressed. Tel: +1 303 315 0427; Fax: +1 303 315 7097; Email: mair.churchill{at}uchsc.edu

Ubiquitous high-mobility-group (HMGB) chromosomal proteins bind DNA in a non-sequence- specific fashion to promote chromatin function and gene regulation. Minor groove DNA binding of the HMG domain induces substantial DNA bending toward the major groove, and several interfacial residues contribute by DNA intercalation. The role of the intercalating residues in DNA binding, bending and specificity was systematically examined for a series of mutant Drosophila HMGB (HMG-D) proteins. The primary intercalating residue of HMG-D, Met13, is required both for high-affinity DNA binding and normal DNA bending. Leu9 and Tyr12 directly interact with Met13 and are required for HMG domain stability in addition to linear DNA binding and bending, which is an important function for these residues. In contrast, DNA binding and bending is retained in truncations of intercalating residues Val32 and Thr33 to alanine, but DNA bending is decreased for the glycine substitutions. Furthermore, substitution of the intercalating residues with those predicted to be involved in the specificity of the HMG domain transcription factors results in increased DNA affinity and decreased DNA bending without increased specificity. These studies reveal the importance of residues that buttress intercalating residues and suggest that features of the HMG domain other than a few base-specific hydrogen bonds distinguish the sequence-specific and non-sequence-specific HMG domain functions.


Add to CiteULike CiteULike   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us    What's this?


This article has been cited by other articles:


Home page
 Nucleic Acids ResHome page
S. C. Roemer, J. Adelman, M. E. A. Churchill, and D. P. Edwards
Mechanism of high-mobility group protein B enhancement of progesterone receptor sequence-specific DNA binding
Nucleic Acids Res., June 1, 2008; 36(11): 3655 - 3666.
[Abstract] [Full Text] [PDF]

Home page
 Biophys. JHome page
M. Zacharias
Minor Groove Deformability of DNA: A Molecular Dynamics Free Energy Simulation Study
Biophys. J., August 1, 2006; 91(3): 882 - 891.
[Abstract] [Full Text] [PDF]

Home page
 Biophys. JHome page
M. McCauley, P. R. Hardwidge, L. J. Maher III, and M. C. Williams
Dual Binding Modes for an HMG Domain from Human HMGB2 on DNA
Biophys. J., July 1, 2005; 89(1): 353 - 364.
[Abstract] [Full Text] [PDF]

Home page
 Nucleic Acids ResHome page
C.-Y. Chen, T.-P. Ko, T.-W. Lin, C.-C. Chou, C.-J. Chen, and A. H.-J. Wang
Probing the DNA kink structure induced by the hyperthermophilic chromosomal protein Sac7d
Nucleic Acids Res., January 14, 2005; 33(1): 430 - 438.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
E. Kamau, K. T. Bauerle, and A. Grove
The Saccharomyces cerevisiae High Mobility Group Box Protein HMO1 Contains Two Functional DNA Binding Domains
J. Biol. Chem., December 31, 2004; 279(53): 55234 - 55240.
[Abstract] [Full Text] [PDF]

Home page
 Mol. Cell. Biol.Home page
M. Ciubotaru and D. G. Schatz
Synapsis of Recombination Signal Sequences Located in cis and DNA Underwinding in V(D)J Recombination
Mol. Cell. Biol., October 1, 2004; 24(19): 8727 - 8744.
[Abstract] [Full Text] [PDF]


Disclaimer:
Please note that abstracts for content published before 1996 were created through digital scanning and may therefore not exactly replicate the text of the original print issues. All efforts have been made to ensure accuracy, but the Publisher will not be held responsible for any remaining inaccuracies. If you require any further clarification, please contact our Customer Services Department.