2h1k
Crystal structure of the Pdx1 homeodomain in complex with DNA
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OverviewOverview
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.
About this StructureAbout this Structure
2H1K is a Single protein structure of sequence from Mesocricetus auratus. Full crystallographic information is available from OCA.
ReferenceReference
Structural basis for induced fit mechanisms in DNA recognition by the Pdx1 homeodomain., Longo A, Guanga GP, Rose RB, Biochemistry. 2007 Mar 20;46(11):2948-57. Epub 2007 Feb 23. PMID:17315980
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