PROSITE documentation PDOC51937HNF-1 dimerization (HNF-p1) domain profile
The homeodomain proteins hepatocyte nuclear factor (HNF)-1α and HNF-1β comprise a functionnally important family in which dimerization is essential for DNA binding. HNF-1α and HNF-1β regulate tissue-specific genes in liver, kidney, intestine, and pancreas. These proteins form homo- and heterodimers through an autonomously folded domain encompassing the 32 N-terminal amino acids (HNF-p1). The dimerization domain also binds the transcriptional coactivator DCoH, which stimulates HNF-1α activity [1,2,3,4,5].
The HNF-p1 dimer folds into an X-type, antiparallel, four-helix bundle (4HB). Each monomer consists of two helices: a longer N-terminal helix and a shorter C-terminal helix, connected by a tight turn unrelated to classical β- or γ-turn families (see <PDB:1G39>). The dimer contains a rigid element, the N-terminal anti-parallel mini-zipper comprising α-helices 1 and 1', and a plastic element, the C-terminal coiled-coil comprising α-helices 2 and 2' [2,3,4,5].
The profile we developed covers the entire HNF-p1 domain.
Last update:August 2020 / First entry.
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PROSITE method (with tools and information) covered by this documentation:
| 1 | Authors | Mendel D.B. Crabtree G.R. |
| Title | HNF-1, a member of a novel class of dimerizing homeodomain proteins. | |
| Source | J. Biol. Chem. 266:677-680(1991). | |
| PubMed ID | 1985954 |
| 2 | Authors | Rose R.B. Bayle J.H. Endrizzi J.A. Cronk J.D. Crabtree G.R. Alber T. |
| Title | Structural basis of dimerization, coactivator recognition and MODY3 mutations in HNF-1alpha. | |
| Source | Nat. Struct. Biol. 7:744-748(2000). | |
| PubMed ID | 10966642 | |
| DOI | 10.1038/78966 |
| 3 | Authors | Rose R.B. Endrizzi J.A. Cronk J.D. Holton J. Alber T. |
| Title | High-resolution structure of the HNF-1alpha dimerization domain. | |
| Source | Biochemistry 39:15062-15070(2000). | |
| PubMed ID | 11106484 | |
| DOI | 10.1021/bi001996t |
| 4 | Authors | Narayana N. Hua Q. Weiss M.A. |
| Title | The dimerization domain of HNF-1alpha: structure and plasticity of an intertwined four-helix bundle with application to diabetes mellitus. | |
| Source | J. Mol. Biol. 310:635-658(2001). | |
| PubMed ID | 11439029 | |
| DOI | 10.1006/jmbi.2001.4780 |
| 5 | Authors | Narayana N. Phillips N.B. Hua Q.X. Jia W. Weiss M.A. |
| Title | Diabetes mellitus due to misfolding of a beta-cell transcription factor: stereospecific frustration of a Schellman motif in HNF-1alpha. | |
| Source | J. Mol. Biol. 362:414-429(2006). | |
| PubMed ID | 16930618 | |
| DOI | 10.1016/j.jmb.2006.06.086 |
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