Structural highlights
Function
[HNF1A_MOUSE] Transcriptional activator that regulates the tissue specific expression of multiple genes, especially in pancreatic islet cells and in liver. Required for the expression of several liver specific genes. Binds to the inverted palindrome 5'-GTTAATNATTAAC-3'.[1] [2]
Evolutionary Conservation
Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.
Publication Abstract from PubMed
The transcription factor LFB1/HNF1 from rat liver nuclei is a 628 amino acid protein that functions as a dimer binding to the inverted palindrome GTTAATN-ATTAAC consensus site. We have crystallized a 99 residue protein containing the homeodomain portion of LFB1, and solved its structure using X-ray diffraction data to 2.8 A resolution. The topology and orientation of the helices is essentially the same as that found in the engrailed, MAT alpha 2 and Antennapedia homeodomains, even though the LFB1 homeodomain contains 21 more residues. The 21 residue insertion is found in an extension of helix 2 and consequent lengthening of the connecting loop between helix 2 and helix 3. Comparison with the engrailed homeodomain-DNA complex indicates that the mode of interaction with DNA is similar in both proteins, with a number of conserved contacts in the major groove. The extra 21 residues of the LFB1 homeodomain are not involved in DNA binding. Binding of the LFB1 dimer to a B-DNA palindromic consensus sequence requires either a conformational change of the DNA (presumably bending), or a rearrangement of the subunits relative to the DNA.
The X-ray structure of an atypical homeodomain present in the rat liver transcription factor LFB1/HNF1 and implications for DNA binding.,Ceska TA, Lamers M, Monaci P, Nicosia A, Cortese R, Suck D EMBO J. 1993 May;12(5):1805-10. PMID:8491173[3]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Servitja JM, Pignatelli M, Maestro MA, Cardalda C, Boj SF, Lozano J, Blanco E, Lafuente A, McCarthy MI, Sumoy L, Guigo R, Ferrer J. Hnf1alpha (MODY3) controls tissue-specific transcriptional programs and exerts opposed effects on cell growth in pancreatic islets and liver. Mol Cell Biol. 2009 Jun;29(11):2945-59. doi: 10.1128/MCB.01389-08. Epub 2009 Mar , 16. PMID:19289501 doi:http://dx.doi.org/10.1128/MCB.01389-08
- ↑ Rose RB, Bayle JH, Endrizzi JA, Cronk JD, Crabtree GR, Alber T. Structural basis of dimerization, coactivator recognition and MODY3 mutations in HNF-1alpha. Nat Struct Biol. 2000 Sep;7(9):744-8. PMID:10966642 doi:10.1038/78966
- ↑ Ceska TA, Lamers M, Monaci P, Nicosia A, Cortese R, Suck D. The X-ray structure of an atypical homeodomain present in the rat liver transcription factor LFB1/HNF1 and implications for DNA binding. EMBO J. 1993 May;12(5):1805-10. PMID:8491173
