Crystallization of hepatocyte nuclear factor 4 alpha (HNF4 alpha) in complex with the HNF1 alpha promoter element. Acta Crystallogr Sect F Struct Biol Cryst Commun 2008 Apr 01;64(Pt 4):313-7
Date
04/09/2008Pubmed ID
18391435Pubmed Central ID
PMC2374247DOI
10.1107/S1744309108007136Scopus ID
2-s2.0-41949119093 (requires institutional sign-in at Scopus site) 8 CitationsAbstract
Hepatocyte nuclear factor 4alpha (HNF4alpha) is a member of the nuclear receptor superfamily that plays a central role in organ development and metabolic functions. Mutations on HNF4alpha 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 HNF4alpha 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, HNF1alpha. The HNF4alpha protein displays a cooperative and specific DNA-binding activity towards its target gene-recognition elements. Crystals of the complex diffract to 2.0 A 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 A, beta = 119.36 degrees . 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.
Author List
Lu P, Liu J, Melikishvili M, Fried MG, Chi YIAuthor
Young-In Chi PhD Assistant Professor in the Surgery department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
Age of OnsetAmino Acid Sequence
Crystallization
Diabetes Mellitus, Type 2
Hepatocyte Nuclear Factor 1-alpha
Hepatocyte Nuclear Factor 4
Humans
Molecular Sequence Data
Promoter Regions, Genetic
Protein Binding
X-Ray Diffraction
