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| | ==Human Pit-1 and 4xCATT DNA complex== | | ==Human Pit-1 and 4xCATT DNA complex== |
| - | <StructureSection load='5wc9' size='340' side='right' caption='[[5wc9]], [[Resolution|resolution]] 3.15Å' scene=''> | + | <StructureSection load='5wc9' size='340' side='right'caption='[[5wc9]], [[Resolution|resolution]] 3.15Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[5wc9]] is a 8 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5WC9 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5WC9 FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[5wc9]] is a 8 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5WC9 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5WC9 FirstGlance]. <br> |
| - | </td></tr><tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">POU1F1, GHF1, PIT1 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr> | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 3.15Å</td></tr> |
| - | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5wc9 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5wc9 OCA], [http://pdbe.org/5wc9 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5wc9 RCSB], [http://www.ebi.ac.uk/pdbsum/5wc9 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5wc9 ProSAT]</span></td></tr> | + | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=5wc9 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5wc9 OCA], [https://pdbe.org/5wc9 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5wc9 RCSB], [https://www.ebi.ac.uk/pdbsum/5wc9 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5wc9 ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | == Disease == | | == Disease == |
| - | [[http://www.uniprot.org/uniprot/PIT1_HUMAN PIT1_HUMAN]] Hypothyroidism due to deficient transcription factors involved in pituitary development or function;Combined pituitary hormone deficiencies, genetic forms. The disease is caused by mutations affecting the gene represented in this entry. | + | [https://www.uniprot.org/uniprot/PIT1_HUMAN PIT1_HUMAN] Hypothyroidism due to deficient transcription factors involved in pituitary development or function;Combined pituitary hormone deficiencies, genetic forms. The disease is caused by mutations affecting the gene represented in this entry. |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/PIT1_HUMAN PIT1_HUMAN]] Transcription factor involved in the specification of the lactotrope, somatotrope, and thyrotrope phenotypes in the developing anterior pituitary. Specifically binds to the consensus sequence 5'-TAAAT-3'. Activates growth hormone and prolactin genes (PubMed:22010633, PubMed:26612202).<ref>PMID:22010633</ref> <ref>PMID:26612202</ref> | + | [https://www.uniprot.org/uniprot/PIT1_HUMAN PIT1_HUMAN] Transcription factor involved in the specification of the lactotrope, somatotrope, and thyrotrope phenotypes in the developing anterior pituitary. Specifically binds to the consensus sequence 5'-TAAAT-3'. Activates growth hormone and prolactin genes (PubMed:22010633, PubMed:26612202).<ref>PMID:22010633</ref> <ref>PMID:26612202</ref> |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Human]] | + | [[Category: Homo sapiens]] |
| - | [[Category: Agarwal, S]] | + | [[Category: Large Structures]] |
| - | [[Category: Cho, T Y]] | + | [[Category: Agarwal S]] |
| - | [[Category: Dna binding protein]] | + | [[Category: Cho TY]] |
| - | [[Category: Dna-protein complex]]
| + | |
| - | [[Category: Transcription regulation]]
| + | |
| Structural highlights
Disease
PIT1_HUMAN Hypothyroidism due to deficient transcription factors involved in pituitary development or function;Combined pituitary hormone deficiencies, genetic forms. The disease is caused by mutations affecting the gene represented in this entry.
Function
PIT1_HUMAN Transcription factor involved in the specification of the lactotrope, somatotrope, and thyrotrope phenotypes in the developing anterior pituitary. Specifically binds to the consensus sequence 5'-TAAAT-3'. Activates growth hormone and prolactin genes (PubMed:22010633, PubMed:26612202).[1] [2]
Publication Abstract from PubMed
Overexpression of the proinflammatory cytokine macrophage migration inhibitory factor (MIF) is linked to a number of autoimmune diseases and cancer. MIF production has been correlated to the number of CATT repeats in a microsatellite region upstream of the MIF gene. We have characterized the interaction of pituitary-specific positive transcription factor 1 (Pit-1) with a portion of the MIF promoter region flanking a microsatellite polymorphism (-794 CATT5-8). Using fluorescence anisotropy, we quantified tight complex formation between Pit-1 and an oligonucleotide consisting of eight consecutive CATT repeats (8xCATT) with an apparent Kd of 35 nM. Using competition experiments we found a 23 base pair oligonucleotide with 4xCATT repeats to be the minimum DNA sequence necessary for high affinity interaction with Pit-1. The stoichiometry of the Pit-1 DNA interaction was determined to be 2:1 and binding is cooperative in nature. We subsequently structurally characterized the complex and discovered a completely novel binding mode for Pit-1 in contrast to previously described Pit-1 complex structures. The affinity of Pit-1 for the CATT target sequence was found to be highly dependent on cooperativity. This work lays the groundwork for understanding transcriptional regulation of MIF and pursuing Pit-1 as a therapeutic target to treat MIF-mediated inflammatory disorders.
Biochemical and structural characterization of a novel cooperative binding mode by Pit-1 with CATT repeats in the macrophage migration inhibitory factor promoter.,Agarwal S, Cho TY Nucleic Acids Res. 2017 Nov 23. pii: 4653535. doi: 10.1093/nar/gkx1183. PMID:29186613[3]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Turton JP, Strom M, Langham S, Dattani MT, Le Tissier P. Two novel mutations in the POU1F1 gene generate null alleles through different mechanisms leading to combined pituitary hormone deficiency. Clin Endocrinol (Oxf). 2012 Mar;76(3):387-93. doi:, 10.1111/j.1365-2265.2011.04236.x. PMID:22010633 doi:http://dx.doi.org/10.1111/j.1365-2265.2011.04236.x
- ↑ Sobrier ML, Tsai YC, Perez C, Leheup B, Bouceba T, Duquesnoy P, Copin B, Sizova D, Penzo A, Stanger BZ, Cooke NE, Liebhaber SA, Amselem S. Functional characterization of a human POU1F1 mutation associated with isolated growth hormone deficiency: a novel etiology for IGHD. Hum Mol Genet. 2016 Feb 1;25(3):472-83. doi: 10.1093/hmg/ddv486. Epub 2015 Nov, 26. PMID:26612202 doi:http://dx.doi.org/10.1093/hmg/ddv486
- ↑ Agarwal S, Cho TY. Biochemical and structural characterization of a novel cooperative binding mode by Pit-1 with CATT repeats in the macrophage migration inhibitory factor promoter. Nucleic Acids Res. 2017 Nov 23. pii: 4653535. doi: 10.1093/nar/gkx1183. PMID:29186613 doi:http://dx.doi.org/10.1093/nar/gkx1183
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