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6mbz

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Structure of Transcription Factor

Structural highlights

6mbz is a 2 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	X-ray diffraction, Resolution 3.21Å
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Disease

STA5B_HUMAN Acute promyelocytic leukemia;Laron syndrome with immunodeficiency. The disease is caused by mutations affecting the gene represented in this entry.

Function

STA5B_HUMAN Carries out a dual function: signal transduction and activation of transcription. Mediates cellular responses to the cytokine KITLG/SCF and other growth factors. Binds to the GAS element and activates PRL-induced transcription. Positively regulates hematopoietic/erythroid differentiation.^[1] ^[2]

Publication Abstract from PubMed

Hyper-activated STAT5B variants are high value oncology targets for pharmacologic intervention. STAT5B(N642H), a frequently-occurring oncogenic driver mutation, promotes aggressive T-cell leukemia/lymphoma in patient carriers, although the molecular origins remain unclear. Herein, we emphasize the aggressive nature of STAT5B(N642H) in driving T-cell neoplasia upon hematopoietic expression in transgenic mice, revealing evidence of multiple T-cell subset organ infiltration. Notably, we demonstrate STAT5B(N642H)-driven transformation of gammadelta T-cells in in vivo syngeneic transplant models, comparable to STAT5B(N642H) patient gammadelta T-cell entities. Importantly, we present human STAT5B and STAT5B(N642H) crystal structures, which propose alternative mutation-mediated SH2 domain conformations. Our biophysical data suggests STAT5B(N642H) can adopt a hyper-activated and hyper-inactivated state with resistance to dephosphorylation. MD simulations support sustained interchain cross-domain interactions in STAT5B(N642H), conferring kinetic stability to the mutant anti-parallel dimer. This study provides a molecular explanation for the STAT5B(N642H) activating potential, and insights into pre-clinical models for targeted intervention of hyper-activated STAT5B.

Structural and functional consequences of the STAT5B(N642H) driver mutation.,de Araujo ED, Erdogan F, Neubauer HA, Meneksedag-Erol D, Manaswiyoungkul P, Eram MS, Seo HS, Qadree AK, Israelian J, Orlova A, Suske T, Pham HTT, Boersma A, Tangermann S, Kenner L, Rulicke T, Dong A, Ravichandran M, Brown PJ, Audette GF, Rauscher S, Dhe-Paganon S, Moriggl R, Gunning PT Nat Commun. 2019 Jun 7;10(1):2517. doi: 10.1038/s41467-019-10422-7. PMID:31175292^[3]

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

References

↑ Vignudelli T, Selmi T, Martello A, Parenti S, Grande A, Gemelli C, Zanocco-Marani T, Ferrari S. ZFP36L1 negatively regulates erythroid differentiation of CD34+ hematopoietic stem cells by interfering with the Stat5b pathway. Mol Biol Cell. 2010 Oct 1;21(19):3340-51. doi: 10.1091/mbc.E10-01-0040. Epub 2010, Aug 11. PMID:20702587 doi:http://dx.doi.org/10.1091/mbc.E10-01-0040
↑ Silva CM, Lu H, Day RN. Characterization and cloning of STAT5 from IM-9 cells and its activation by growth hormone. Mol Endocrinol. 1996 May;10(5):508-18. doi: 10.1210/mend.10.5.8732682. PMID:8732682 doi:http://dx.doi.org/10.1210/mend.10.5.8732682
↑ de Araujo ED, Erdogan F, Neubauer HA, Meneksedag-Erol D, Manaswiyoungkul P, Eram MS, Seo HS, Qadree AK, Israelian J, Orlova A, Suske T, Pham HTT, Boersma A, Tangermann S, Kenner L, Rulicke T, Dong A, Ravichandran M, Brown PJ, Audette GF, Rauscher S, Dhe-Paganon S, Moriggl R, Gunning PT. Structural and functional consequences of the STAT5B(N642H) driver mutation. Nat Commun. 2019 Jun 7;10(1):2517. doi: 10.1038/s41467-019-10422-7. PMID:31175292 doi:http://dx.doi.org/10.1038/s41467-019-10422-7

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

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/6mbz"

Categories: Homo sapiens | Large Structures | Dhe-Paganon S | Seo H-S

@@ Line 3: / Line 3: @@
 <StructureSection load='6mbz' size='340' side='right'caption='[[6mbz]], [[Resolution|resolution]] 3.21&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[6mbz]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6MBZ OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6MBZ FirstGlance]. <br>
+<table><tr><td colspan='2'>[[6mbz]] is a 2 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=6MBZ OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6MBZ FirstGlance]. <br>
-</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=6mbz FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6mbz OCA], [http://pdbe.org/6mbz PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6mbz RCSB], [http://www.ebi.ac.uk/pdbsum/6mbz PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6mbz ProSAT]</span></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]] 3.21&#8491;</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=6mbz FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6mbz OCA], [https://pdbe.org/6mbz PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6mbz RCSB], [https://www.ebi.ac.uk/pdbsum/6mbz PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6mbz ProSAT]</span></td></tr>
 </table>
 == Disease ==
-[[http://www.uniprot.org/uniprot/STA5B_HUMAN STA5B_HUMAN]] Acute promyelocytic leukemia;Laron syndrome with immunodeficiency. The disease is caused by mutations affecting the gene represented in this entry.
+[https://www.uniprot.org/uniprot/STA5B_HUMAN STA5B_HUMAN] Acute promyelocytic leukemia;Laron syndrome with immunodeficiency. The disease is caused by mutations affecting the gene represented in this entry.
 == Function ==
-[[http://www.uniprot.org/uniprot/STA5B_HUMAN STA5B_HUMAN]] Carries out a dual function: signal transduction and activation of transcription. Mediates cellular responses to the cytokine KITLG/SCF and other growth factors. Binds to the GAS element and activates PRL-induced transcription. Positively regulates hematopoietic/erythroid differentiation.<ref>PMID:20702587</ref> <ref>PMID:8732682</ref>
+[https://www.uniprot.org/uniprot/STA5B_HUMAN STA5B_HUMAN] Carries out a dual function: signal transduction and activation of transcription. Mediates cellular responses to the cytokine KITLG/SCF and other growth factors. Binds to the GAS element and activates PRL-induced transcription. Positively regulates hematopoietic/erythroid differentiation.<ref>PMID:20702587</ref> <ref>PMID:8732682</ref>
 <div style="background-color:#fffaf0;">
 == Publication Abstract from PubMed ==
@@ Line 23: / Line 24: @@
 __TOC__
 </StructureSection>
+[[Category: Homo sapiens]]
 [[Category: Large Structures]]
-[[Category: Dhe-Paganon, S]]
+[[Category: Dhe-Paganon S]]
-[[Category: Seo, H S]]
+[[Category: Seo H-S]]
-[[Category: Transcription activator]]
-[[Category: Transcription factor]]

6mbz

From Proteopedia

Current revision

Structure of Transcription Factor

Structural highlights

Disease

Function

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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