5cc0

From Proteopedia

(Difference between revisions)

Revision as of 11:57, 14 June 2023

AncSR2 - TSLP nGRE complex

Structural highlights

5cc0 is a 4 chain structure with sequence from Homo sapiens and Synthetic construct. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

PRGR_HUMAN The steroid hormones and their receptors are involved in the regulation of eukaryotic gene expression and affect cellular proliferation and differentiation in target tissues. Progesterone receptor isoform B (PRB) is involved activation of c-SRC/MAPK signaling on hormone stimulation.^[1] ^[2] ^[3] ^[4] ^[5] ^[6] ^[7] Isoform A is inactive in stimulating c-Src/MAPK signaling on hormone stimulation.^[8] ^[9] ^[10] ^[11] ^[12] ^[13] ^[14]

Publication Abstract from PubMed

Many genomes contain families of paralogs--proteins with divergent function that evolved from a common ancestral gene after a duplication event. To understand how paralogous transcription factors evolve divergent DNA specificities, we examined how the glucocorticoid receptor and its paralogs evolved to bind activating response elements [(+)GREs] and negative glucocorticoid response elements (nGREs). We show that binding to nGREs is a property of the glucocorticoid receptor (GR) DNA-binding domain (DBD) not shared by other members of the steroid receptor family. Using phylogenetic, structural, biochemical, and molecular dynamics techniques, we show that the ancestral DBD from which GR and its paralogs evolved was capable of binding both nGRE and (+)GRE sequences because of the ancestral DBD's ability to assume multiple DNA-bound conformations. Subsequent amino acid substitutions in duplicated daughter genes selectively restricted protein conformational space, causing this dual DNA-binding specificity to be selectively enhanced in the GR lineage and lost in all others. Key substitutions that determined the receptors' response element-binding specificity were far from the proteins' DNA-binding interface and interacted epistatically to change the DBD's function through DNA-induced allosteric mechanisms. These amino acid substitutions subdivided both the conformational and functional space of the ancestral DBD among the present-day receptors, allowing a paralogous family of transcription factors to control disparate transcriptional programs despite high sequence identity.

Distal substitutions drive divergent DNA specificity among paralogous transcription factors through subdivision of conformational space.,Hudson WH, Kossmann BR, de Vera IM, Chuo SW, Weikum ER, Eick GN, Thornton JW, Ivanov IN, Kojetin DJ, Ortlund EA Proc Natl Acad Sci U S A. 2016 Jan 12;113(2):326-31. doi:, 10.1073/pnas.1518960113. Epub 2015 Dec 29. PMID:26715749^[15]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Pierson-Mullany LK, Lange CA. Phosphorylation of progesterone receptor serine 400 mediates ligand-independent transcriptional activity in response to activation of cyclin-dependent protein kinase 2. Mol Cell Biol. 2004 Dec;24(24):10542-57. PMID:15572662 doi:10.1128/MCB.24.24.10542-10557.2004
↑ Narayanan R, Edwards DP, Weigel NL. Human progesterone receptor displays cell cycle-dependent changes in transcriptional activity. Mol Cell Biol. 2005 Apr;25(8):2885-98. PMID:15798179 doi:25/8/2885
↑ Man JH, Li HY, Zhang PJ, Zhou T, He K, Pan X, Liang B, Li AL, Zhao J, Gong WL, Jin BF, Xia Q, Yu M, Shen BF, Zhang XM. PIAS3 induction of PRB sumoylation represses PRB transactivation by destabilizing its retention in the nucleus. Nucleic Acids Res. 2006;34(19):5552-66. Epub 2006 Oct 4. PMID:17020914 doi:gkl691
↑ Zhang PJ, Zhao J, Li HY, Man JH, He K, Zhou T, Pan X, Li AL, Gong WL, Jin BF, Xia Q, Yu M, Shen BF, Zhang XM. CUE domain containing 2 regulates degradation of progesterone receptor by ubiquitin-proteasome. EMBO J. 2007 Apr 4;26(7):1831-42. Epub 2007 Mar 8. PMID:17347654 doi:7601602
↑ Daniel AR, Faivre EJ, Lange CA. Phosphorylation-dependent antagonism of sumoylation derepresses progesterone receptor action in breast cancer cells. Mol Endocrinol. 2007 Dec;21(12):2890-906. Epub 2007 Aug 23. PMID:17717077 doi:me.2007-0248
↑ Daniel AR, Qiu M, Faivre EJ, Ostrander JH, Skildum A, Lange CA. Linkage of progestin and epidermal growth factor signaling: phosphorylation of progesterone receptors mediates transcriptional hypersensitivity and increased ligand-independent breast cancer cell growth. Steroids. 2007 Feb;72(2):188-201. Epub 2006 Dec 14. PMID:17173941 doi:S0039-128X(06)00225-X
↑ Faivre EJ, Daniel AR, Hillard CJ, Lange CA. Progesterone receptor rapid signaling mediates serine 345 phosphorylation and tethering to specificity protein 1 transcription factors. Mol Endocrinol. 2008 Apr;22(4):823-37. Epub 2008 Jan 17. PMID:18202149 doi:me.2007-0437
↑ Pierson-Mullany LK, Lange CA. Phosphorylation of progesterone receptor serine 400 mediates ligand-independent transcriptional activity in response to activation of cyclin-dependent protein kinase 2. Mol Cell Biol. 2004 Dec;24(24):10542-57. PMID:15572662 doi:10.1128/MCB.24.24.10542-10557.2004
↑ Narayanan R, Edwards DP, Weigel NL. Human progesterone receptor displays cell cycle-dependent changes in transcriptional activity. Mol Cell Biol. 2005 Apr;25(8):2885-98. PMID:15798179 doi:25/8/2885
↑ Man JH, Li HY, Zhang PJ, Zhou T, He K, Pan X, Liang B, Li AL, Zhao J, Gong WL, Jin BF, Xia Q, Yu M, Shen BF, Zhang XM. PIAS3 induction of PRB sumoylation represses PRB transactivation by destabilizing its retention in the nucleus. Nucleic Acids Res. 2006;34(19):5552-66. Epub 2006 Oct 4. PMID:17020914 doi:gkl691
↑ Zhang PJ, Zhao J, Li HY, Man JH, He K, Zhou T, Pan X, Li AL, Gong WL, Jin BF, Xia Q, Yu M, Shen BF, Zhang XM. CUE domain containing 2 regulates degradation of progesterone receptor by ubiquitin-proteasome. EMBO J. 2007 Apr 4;26(7):1831-42. Epub 2007 Mar 8. PMID:17347654 doi:7601602
↑ Daniel AR, Faivre EJ, Lange CA. Phosphorylation-dependent antagonism of sumoylation derepresses progesterone receptor action in breast cancer cells. Mol Endocrinol. 2007 Dec;21(12):2890-906. Epub 2007 Aug 23. PMID:17717077 doi:me.2007-0248
↑ Daniel AR, Qiu M, Faivre EJ, Ostrander JH, Skildum A, Lange CA. Linkage of progestin and epidermal growth factor signaling: phosphorylation of progesterone receptors mediates transcriptional hypersensitivity and increased ligand-independent breast cancer cell growth. Steroids. 2007 Feb;72(2):188-201. Epub 2006 Dec 14. PMID:17173941 doi:S0039-128X(06)00225-X
↑ Faivre EJ, Daniel AR, Hillard CJ, Lange CA. Progesterone receptor rapid signaling mediates serine 345 phosphorylation and tethering to specificity protein 1 transcription factors. Mol Endocrinol. 2008 Apr;22(4):823-37. Epub 2008 Jan 17. PMID:18202149 doi:me.2007-0437
↑ Hudson WH, Kossmann BR, de Vera IM, Chuo SW, Weikum ER, Eick GN, Thornton JW, Ivanov IN, Kojetin DJ, Ortlund EA. Distal substitutions drive divergent DNA specificity among paralogous transcription factors through subdivision of conformational space. Proc Natl Acad Sci U S A. 2016 Jan 12;113(2):326-31. doi:, 10.1073/pnas.1518960113. Epub 2015 Dec 29. PMID:26715749 doi:http://dx.doi.org/10.1073/pnas.1518960113

1 Structural highlights
2 Function
3 Publication Abstract from PubMed
4 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/5cc0"

Categories: Homo sapiens | Large Structures | Synthetic construct | Hudson WH | Ortlund EA

@@ Line 3: / Line 3: @@
 <StructureSection load='5cc0' size='340' side='right'caption='[[5cc0]], [[Resolution|resolution]] 2.41&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[5cc0]] is a 4 chain structure with sequence from [http://en.wikipedia.org/wiki/Synthetic_construct_sequences Synthetic construct sequences]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5CC0 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5CC0 FirstGlance]. <br>
+<table><tr><td colspan='2'>[[5cc0]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [https://en.wikipedia.org/wiki/Synthetic_construct Synthetic construct]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5CC0 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5CC0 FirstGlance]. <br>
-</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr>
+</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr>
-<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[5cbx|5cbx]], [[5cby|5cby]], [[5cbz|5cbz]], [[5cc1|5cc1]]</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=5cc0 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5cc0 OCA], [https://pdbe.org/5cc0 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5cc0 RCSB], [https://www.ebi.ac.uk/pdbsum/5cc0 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5cc0 ProSAT]</span></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=5cc0 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5cc0 OCA], [http://pdbe.org/5cc0 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5cc0 RCSB], [http://www.ebi.ac.uk/pdbsum/5cc0 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5cc0 ProSAT]</span></td></tr>
 </table>
+== Function ==
+[https://www.uniprot.org/uniprot/PRGR_HUMAN PRGR_HUMAN] The steroid hormones and their receptors are involved in the regulation of eukaryotic gene expression and affect cellular proliferation and differentiation in target tissues. Progesterone receptor isoform B (PRB) is involved activation of c-SRC/MAPK signaling on hormone stimulation.<ref>PMID:15572662</ref> <ref>PMID:15798179</ref> <ref>PMID:17020914</ref> <ref>PMID:17347654</ref> <ref>PMID:17717077</ref> <ref>PMID:17173941</ref> <ref>PMID:18202149</ref>   Isoform A is inactive in stimulating c-Src/MAPK signaling on hormone stimulation.<ref>PMID:15572662</ref> <ref>PMID:15798179</ref> <ref>PMID:17020914</ref> <ref>PMID:17347654</ref> <ref>PMID:17717077</ref> <ref>PMID:17173941</ref> <ref>PMID:18202149</ref>
 <div style="background-color:#fffaf0;">
 == Publication Abstract from PubMed ==
@@ Line 21: / Line 22: @@
 __TOC__
 </StructureSection>
+[[Category: Homo sapiens]]
 [[Category: Large Structures]]
-[[Category: Synthetic construct sequences]]
+[[Category: Synthetic construct]]
-[[Category: Hudson, W H]]
+[[Category: Hudson WH]]
-[[Category: Ortlund, E A]]
+[[Category: Ortlund EA]]
-[[Category: Dna binding protein-dna complex]]
-[[Category: Dna binding protein]]

5cc0

From Proteopedia

Revision as of 11:57, 14 June 2023

AncSR2 - TSLP nGRE complex

Structural highlights

Function

Publication Abstract from PubMed

References

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Proteopedia Page Contributors and Editors (what is this?)

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