PDBsum entry 2h8r

Transcription activator/DNA

PDB id: 2h8r

Contents

Protein chains

176 a.a. *

DNA/RNA

Waters ×7

* Residue conservation analysis

PDB id:

2h8r

Name:

Transcription activator/DNA

Title:

Hepatocyte nuclear factor 1b bound to dna: mody5 gene product

Structure:

5'-d( Cp Tp Tp Gp Gp Tp Tp Ap Ap Tp Ap Ap Tp Tp Cp Ap Cp Cp Ap G)-3'. Chain: e. Engineered: yes. 5'-d( Gp Cp Tp Gp Gp Tp Gp Ap Ap Tp Tp Ap Tp Tp Ap Ap Cp Cp Ap A)-3'. Chain: f. Engineered: yes. Hepatocyte nuclear factor 1-beta.

Source:

Synthetic: yes. Homo sapiens. Human. Organism_taxid: 9606. Expressed in: escherichia coli bl21(de3). Expression_system_taxid: 469008.

Resolution:

3.20Å R-factor: 0.226 R-free: 0.290

Authors:

P.Lu,G.B.Rha,Y.I.Chi

Key ref:

P.Lu et al. (2007). Structural basis of disease-causing mutations in hepatocyte nuclear factor 1beta. Biochemistry, 46, 12071-12080. PubMed id: 17924661

Date:

07-Jun-06 Release date: 19-Jun-07

Protein chains

P35680  (HNF1B_HUMAN) -  Hepatocyte nuclear factor 1-beta from Homo sapiens

Seq: 557 a.a.

Struc: 176 a.a.*

* PDB and UniProt seqs differ at 1 residue position (black cross)

DNA/RNA chains

C-T-T-G-G-T-T-A-A-T-A-A-T-T-C-A-C-C-A-G 20 bases

G-C-T-G-G-T-G-A-A-T-T-A-T-T-A-A-C-C-A-A 20 bases

Biochemistry 46:12071-12080 (2007)

PubMed id: 17924661

Structural basis of disease-causing mutations in hepatocyte nuclear factor 1beta.

P.Lu, G.B.Rha, Y.I.Chi.

ABSTRACT

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.