View source for 6dmx


==HBZ56 in complex with KIX and c-Myb==
<StructureSection load='6dmx' size='340' side='right'caption='[[6dmx]], [[Resolution|resolution]] 2.80&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[6dmx]] is a 10 chain structure with sequence from [https://en.wikipedia.org/wiki/Human_T-cell_leukemia_virus_type_I Human T-cell leukemia virus type I] and [https://en.wikipedia.org/wiki/Mus_musculus Mus musculus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6DMX OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6DMX FirstGlance]. <br>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.8&#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=6dmx FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6dmx OCA], [https://pdbe.org/6dmx PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6dmx RCSB], [https://www.ebi.ac.uk/pdbsum/6dmx PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6dmx ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/HBZ_HTL1A HBZ_HTL1A] Contributes to the regulation of viral RNA transcription by interacting with host proteins involved in transcriptional activation such as ATF4, or CREB1, and by inhibiting their activity. Additionally, HBZ suppresses host NF-kappa-B-driven transcription mediated by host RELA as well as transcription of some classical NF-kappa-B target genes, including IL8, IL2RA, IRF4, VCAM1, and VEGFA.<ref>PMID:19064727</ref> 
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
The human T cell leukemia virus I basic leucine zipper protein (HTLV-1 HBZ) maintains chronic viral infection and promotes leukemogenesis through poorly understood mechanisms involving interactions with the KIX domain of the transcriptional coactivator CBP and its paralog p300. The KIX domain binds regulatory proteins at the distinct MLL and c-Myb/pKID sites to form binary or ternary complexes. The intrinsically disordered N-terminal activation domain of HBZ (HBZ AD) deregulates cellular signaling pathways by competing directly with cellular and viral transcription factors for binding to the MLL site and by allosterically perturbing binding of the transactivation domain of the hematopoietic transcription factor c-Myb. Crystal structures of the ternary KIX:c-Myb:HBZ complex show that the HBZ AD recruits two KIX:c-Myb entities through tandem amphipathic motifs (L/V)(V/L)DGLL and folds into a long alpha-helix upon binding. Isothermal titration calorimetry reveals strong cooperativity in binding of the c-Myb activation domain to the KIX:HBZ complex and in binding of HBZ to the KIX:c-Myb complex. In addition, binding of KIX to the two HBZ (V/L)DGLL motifs is cooperative; the structures suggest that this cooperativity is achieved through propagation of the HBZ alpha-helix beyond the first binding motif. Our study suggests that the unique structural flexibility and the multiple interaction motifs of the intrinsically disordered HBZ AD are responsible for its potency in hijacking KIX-mediated transcription pathways. The KIX:c-Myb:HBZ complex provides an example of cooperative stabilization in a transcription factor:coactivator network and gives insights into potential mechanisms through which HBZ dysregulates hematopoietic transcriptional programs and promotes T cell proliferation.

Structural basis for cooperative regulation of KIX-mediated transcription pathways by the HTLV-1 HBZ activation domain.,Yang K, Stanfield RL, Martinez-Yamout MA, Dyson HJ, Wilson IA, Wright PE Proc Natl Acad Sci U S A. 2018 Sep 19. pii: 1810397115. doi:, 10.1073/pnas.1810397115. PMID:30232260<ref>PMID:30232260</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 6dmx" style="background-color:#fffaf0;"></div>

==See Also==
*[[CREB-binding protein 3D structures|CREB-binding protein 3D structures]]
*[[Transcriptional activator 3D structures|Transcriptional activator 3D structures]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Human T-cell leukemia virus type I]]
[[Category: Large Structures]]
[[Category: Mus musculus]]
[[Category: Stanfield RL]]
[[Category: Wright PE]]
[[Category: Yang K]]