Structural basis of disease-causing mutations in hepatocyte nuclear factor 1beta. Biochemistry 2007 Oct 30;46(43):12071-80
Date
10/11/2007Pubmed ID
17924661Pubmed Central ID
PMC2367142DOI
10.1021/bi7010527Scopus ID
2-s2.0-35648988438 (requires institutional sign-in at Scopus site) 36 CitationsAbstract
HNF1beta is an atypical POU transcription factor that participates in a hierarchical network of transcription factors controlling the development and proper function of vital organs such as liver, pancreas, and kidney. Many inheritable mutations on HNF1beta are the monogenic causes of diabetes and several kidney diseases. To elucidate the molecular mechanism of its function and the structural basis of mutations, we have determined the crystal structure of human HNF1beta DNA binding domain in complex with a high-affinity promoter. Disease-causing mutations have been mapped to our structure, and their predicted effects have been tested by a set of biochemical/ functional studies. These findings together with earlier findings with a homologous protein HNF1alpha, help us to understand the structural basis of promoter recognition by these atypical POU transcription factors and the site-specific functional disruption by disease-causing mutations.
Author List
Lu P, Rha GB, 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
Amino Acid SequenceElectrophoretic Mobility Shift Assay
HeLa Cells
Hepatocyte Nuclear Factor 1-beta
Humans
Models, Molecular
Molecular Sequence Data
Mutagenesis, Site-Directed
Mutation
Protein Conformation
Sequence Homology, Amino Acid
