1AU7

PIT-1 MUTANT/DNA COMPLEX

Summary for 1AU7

• Entry DOI: 10.2210/pdb1au7/pdb
• Descriptor: CONSENSUS DNA 25-MER, DNA (5'-D(*CP*TP*TP*CP*CP*TP*CP*AP*TP*GP*TP*AP*TP*AP*TP*AP*C P*AP*TP*GP*AP*GP* GP*A)-3'), PROTEIN PIT-1, ... (4 entities in total)
• Functional Keywords: complex (dna-binding protein-dna), pituitary, cphd, pou domain, transcription factor, transcription-dna complex, transcription/dna
• Biological source: Rattus norvegicus (Norway rat)
• Cellular location: Nucleus: P10037
• Total number of polymer chains: 4
• Total formula weight: 49072.92

Authors

Jacobson, E.M.,Li, P.,Leon-Del-Rio, A.,Rosenfeld, M.G.,Aggarwal, A.K. (deposition date: 1997-09-12, release date: 1998-01-28, Last modification date: 2024-02-07)

Primary citation

Jacobson, E.M.,Li, P.,Leon-del-Rio, A.,Rosenfeld, M.G.,Aggarwal, A.K.
Structure of Pit-1 POU domain bound to DNA as a dimer: unexpected arrangement and flexibility.
Genes Dev., 11:198-212, 1997

PubMed Abstract: Pit-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.

PubMed: 9009203

Experimental method

X-RAY DIFFRACTION (2.3 Å)