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J. Biol. Chem., Vol. 278, Issue 2, 1053-1058, January 10, 2003

This Article Full Text Full Text (PDF) All Versions of this Article: 278/2/1053    most recent M207504200v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Sprules, T. Articles by Gehring, K. Search for Related Content PubMed PubMed Citation Articles by Sprules, T. Articles by Gehring, K. Social Bookmarking                      What's this?

Lock and Key Binding of the HOX YPWM Peptide to the PBX Homeodomain^*

Tara Sprules^§, Nancy Green^¶, Mark Featherstone^¶, and Kalle Gehring^**

From the  Department of Biochemistry, ^¶ McGill Cancer Centre,  Department of Chemistry, and ^** Montreal Joint Centre for Structural Biology, McGill University, Montreal, Quebec H3G 1Y6, Canada

HOX homeodomain proteins bind short core DNA sequences to control very specific developmental processes. DNA binding affinity and sequence selectivity are increased by the formation of cooperative complexes with the PBX homeodomain protein. A conserved YPWM motif in the HOX protein is necessary for cooperative binding with PBX. We have determined the structure of a PBX homeodomain bound to a 14-mer DNA duplex. A relaxation-optimized procedure was developed to measure DNA residual dipolar couplings at natural abundance in the 20-kDa binary complex. When the PBX homeodomain binds to DNA, a fourth -helix is formed in the homeodomain. This helix rigidifies the DNA recognition helix of PBX and forms a hydrophobic binding site for the HOX YPWM peptide. The HOX peptide itself shows some structure in solution and suggests that the interaction between PBX and HOX is an example of "lock and key" binding. The NMR structure explains the requirement of DNA for the PBX-HOX interaction and the increased affinity of DNA binding.

The atomic coordinates for the PBX-DNA complex (code 1LFU) have been deposited in the Protein Data Bank, Research Collaboratory for Structural Bioinformatics, Rutgers University, New Brunswick, NJ (http://www.rcsb.org/).

Chemical shifts have been deposited in the BioMagnetic Resonance Bank (code 5349), University of Wisconsin, Madison, WI (www.bmrb.wisc.edu/).

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