Crystallization of hepatocyte nuclear factor 4α (HNF4α) in complex with the HNF1α promoter element

Peng Lu, Jianguo Liu, Manana Melikishvili, Michael G. Fried, Young In Chi

Research output: Contribution to journalArticlepeer-review

7 Scopus citations

Abstract

Hepatocyte nuclear factor 4α (HNF4α) is a member of the nuclear receptor superfamily that plays a central role in organ development and metabolic functions. Mutations on HNF4α cause maturity-onset diabetes of the young (MODY), a dominant monogenic cause of diabetes. In order to understand the molecular mechanism of promoter recognition and the molecular basis of disease-causing mutations, the recombinant HNF4α DNA-binding domain was prepared and used in a study of its binding properties and in crystallization with a 21-mer DNA fragment that contains the promoter element of another MODY gene, HNF1α. The HNF4α protein displays a cooperative and specific DNA-binding activity towards its target gene-recognition elements. Crystals of the complex diffract to 2.0 Å using a synchrotron-radiation source under cryogenic (100 K) conditions and belong to space group C2, with unit-cell parameters a = 121.63, b = 35.43, c = 70.99 Å, β = 119.36°. A molecular-replacement solution has been obtained and structure refinement is in progress. This structure and the binding studies will provide the groundwork for detailed functional and biochemical studies of the MODY mutants.

Original languageEnglish (US)
Pages (from-to)313-317
Number of pages5
JournalActa Crystallographica Section F: Structural Biology and Crystallization Communications
Volume64
Issue number4
DOIs
StatePublished - Mar 29 2008

Keywords

  • Diabetes
  • Gel-shift assay
  • Nuclear receptors
  • Protein-DNA complex
  • Zinc-finger proteins

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