2H1K

Crystal structure of the Pdx1 homeodomain in complex with DNA

Summary for 2H1K

• Entry DOI: 10.2210/pdb2h1k/pdb
• Descriptor: 15-mer DNA, Pancreatic and duodenal homeobox 1, ... (4 entities in total)
• Functional Keywords: protein-dna complex, transcription-dna complex, transcription/dna
• Biological source: Mesocricetus auratus (golden hamster)
• Cellular location: Nucleus (By similarity): P70118
• Total number of polymer chains: 6
• Total formula weight: 34122.45

Authors

Longo, A.,Guanga, G.P.,Rose, R.B. (deposition date: 2006-05-16, release date: 2007-03-20, Last modification date: 2023-08-30)

Primary citation

Longo, A.,Guanga, G.P.,Rose, R.B.
Structural basis for induced fit mechanisms in DNA recognition by the pdx1 homeodomain
Biochemistry, 46:2948-2957, 2007

PubMed Abstract: Pancreatic and duodenal homeobox 1 (Pdx1) is a homeodomain transcription factor belonging to the ParaHox family. Pdx1 plays an essential role in pancreatic endocrine and exocrine cell development and maintenance of adult islet beta-cell function. Mutations in the human pdx1 gene are linked to an early onset form of non-insulin-dependent diabetes mellitus, MODY-4. We demonstrate that the homeodomain reproduces the binding specificity of the full-length protein. We report the 2.4 A resolution crystal structure of the homeodomain bound to a target DNA. The two Pdx1/DNA complexes in the asymmetric unit display conformational differences: in the DNA curvature, the orientation of the homeodomain in the major groove, and the order of the N-terminal arm. Comparing the two complexes indicates invariant protein-DNA contacts, and variant contacts that are unique to each binding orientation. An induced fit model is proposed that depends on the DNA conformation and provides a mechanism for nonlocal contributions to binding specificity.

PubMed: 17315980
DOI: 10.1021/bi060969l

Experimental method

X-RAY DIFFRACTION (2.42 Å)