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Investigating Protein Sequence-structure-dynamics Relationships with Bio3D-web
Published on: July 16, 2017
High-resolution structure of the HNF-1alpha dimerization domain
R B Rose1, J A Endrizzi, J D Cronk
1Department of Molecular and Cell Biology, 229 Stanley Hall #3206, University of California, Berkeley, California 94720-3206, USA.
Biochemistry
|December 7, 2000
Summary
The structure of the HNF-1alpha dimerization domain reveals a four-helix bundle crucial for DNA binding and coactivator interaction. This finding offers insights into MODY3 diabetes mutations.
Area of Science:
- Structural biology
- Molecular biology
- Genetics
Background:
- The N-terminal dimerization domain of hepatocyte nuclear factor-1alpha (HNF-1alpha) is vital for DNA binding and coactivator DCoH association.
- Understanding HNF-1alpha dimerization is key to its function in gene regulation.
Purpose of the Study:
- To elucidate the structural basis of HNF-1alpha dimerization.
- To investigate the structural interactions between HNF-1alpha and DCoH.
- To provide structural insights into MODY3-associated mutations.
Main Methods:
- Determined the 1.2 A resolution X-ray crystal structure of the HNF-1alpha dimerization domain (HNF-p1).
- Utilized Fmoc-selenomethionine synthesis for X-ray crystallography phasing.
- Analyzed three different crystal forms of HNF-p1.
Main Results:
- The HNF-1 dimerization domain adopts a unique four-helix bundle structure.
- This structure is largely conserved in the DCoH complex, with minor conformational shifts.
- Dimerization occurs via an exposed hydrophobic surface, which also serves as the DCoH binding site.
- Conserved residues in HNF-1beta dimerization domain explain heterodimerization.
- Structural data offers insights into three MODY3 mutations.
Conclusions:
- The HNF-1alpha dimerization domain structure provides a molecular basis for dimerization and DCoH interaction.
- The findings rationalize HNF-1alpha/HNF-1beta heterodimerization and offer mechanistic understanding of MODY3 mutations.
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