1au7
PIT-1 MUTANT/DNA COMPLEXPIT-1 MUTANT/DNA COMPLEX
Structural highlights
Function[PIT1_RAT] Transcription factor involved in the specification of the lactotrope, somatotrope, and thyrotrope phenotypes in the developing anterior pituitary. Activates growth hormone and prolactin genes. Specifically binds to the consensus sequence 5'-TAAAT-3'. 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 PubMedPit-1, a member of the POU domain family of transcription factors, characterized by a bipartite DNA-binding domain, serves critical developmental functions based on binding to diverse DNA elements in its target genes. Here we report a high resolution X-ray analysis of the Pit-1 POU domain bound to a DNA element as a homodimer. This analysis reveals that Pit-1 subdomains bind to perpendicular faces of the DNA, rather than opposite faces of the DNA as in Oct-1. This is accomplished by different spacing and orientation of the POU-specific domain. Contrary to previous predictions, the dimerization interface involves the carboxyl terminus of the DNA recognition helix of the homeodomain, which in an extended conformation interacts with specific residues at the amino terminus of helix alpha1 and in the loop between helices alpha3 and alpha4 of the POU-specific domain of the symmetry related monomer. These features suggest the molecular basis of disease-causing mutations in Pit-1 and provide potential basis for the flexible allostery between protein domains and DNA sites in the activation of target genes. Structure of Pit-1 POU domain bound to DNA as a dimer: unexpected arrangement and flexibility.,Jacobson EM, Li P, Leon-del-Rio A, Rosenfeld MG, Aggarwal AK Genes Dev. 1997 Jan 15;11(2):198-212. PMID:9009203[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences |
| ||||||||||||||||