3rkq
From Proteopedia
NKX2.5 Homeodomain dimer bound to ANF-242 DNA
Structural highlights
Disease[NKX25_HUMAN] Athyreosis;Familial isolated congenital asplenia;Atrial septal defect - atrioventricular conduction defects;Atrial septal defect, ostium secundum type;Hypoplastic left heart syndrome;Tetralogy of Fallot;Familial atrial fibrillation;Familial progressive cardiac conduction defect;Thyroid hypoplasia;Ventricular septal defect. The disease is caused by mutations affecting the gene represented in this entry. The disease is caused by mutations affecting the gene represented in this entry. The disease is caused by mutations affecting the gene represented in this entry. The disease is caused by mutations affecting the gene represented in this entry. The disease is caused by mutations affecting the gene represented in this entry. The disease is caused by mutations affecting the gene represented in this entry. The disease is caused by mutations affecting the gene represented in this entry. Function[NKX25_HUMAN] Implicated in commitment to and/or differentiation of the myocardial lineage. Acts as a transcriptional activator of ANF in cooperation with GATA4 (By similarity). It is transcriptionally controlled by PBX1 and acts as a transcriptional repressor of CDKN2B (By similarity). It is required for spleen development.[1] Publication Abstract from PubMedNKX2.5 is a homeodomain containing transcription factor regulating cardiac formation and function, and its mutations are linked to congenital heart disease. Here we provide the first report of the crystal structure of the NKX2.5 homeodomain in complex with double-stranded DNA of its endogenous target, locating within the proximal promoter -242 site of the atrial natriuretic factor gene. The crystal structure, determined at 1.8 A resolution, demonstrates that NKX2.5 homeodomains occupy both DNA binding sites separated by five nucleotides without physical interaction between themselves. The two homeodomains show identical conformation despite the differences in the DNA sequences they bind, and no significant bending of the DNA was observed. Tyr54, absolutely conserved in NK2 family proteins, mediates sequence-specific interaction with the TAAG motif. This high resolution crystal structure of NKX2.5 protein provides a detailed picture of protein and DNA interactions, which allows us to predict DNA binding of mutants identified in human patients. Crystal structure of the human NKX2.5 homeodomain in complex with DNA target.,Pradhan L, Genis C, Scone P, Weinberg EO, Kasahara H, Nam HJ Biochemistry. 2012 Aug 14;51(32):6312-9. Epub 2012 Aug 3. PMID:22849347[2] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
| ||||||||||||||||||||
