1lfu | pdb_00001lfu
NMR Solution Stucture of the Extended PBX Homeodomain Bound to DNA
Structural highlights
Function[PBX1_MOUSE] Plays a role in the cAMP-dependent regulation of CYP17 gene expression via its cAMP-regulatory sequence (CRS1) 5'-ATCAATCAA-3'. Acts as a transcriptional activator of PF4 in complex with MEIS1. May have a role in steroidogenesis and, subsequently, sexual development and differentiation. Isoform PBX1b as part of a PDX1:PBX1b:MEIS2b complex in pancreatic acinar cells is involved in the transcriptional activation of the ELA1 enhancer; the complex binds to the enhancer B element and cooperates with the transcription factor 1 complex (PTF1) bound to the enhancer A element. Probably in complex with MEIS2, is involved in transcriptional regulation by KLF4. Evolutionary Conservation Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf. Publication Abstract from PubMedHOX 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 alpha-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. Lock and key binding of the HOX YPWM peptide to the PBX homeodomain.,Sprules T, Green N, Featherstone M, Gehring K J Biol Chem. 2003 Jan 10;278(2):1053-8. Epub 2002 Oct 29. PMID:12409300[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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