Structural basis for cooperative regulation of KIX-mediated transcription pathways by the HTLV-1 HBZ activation domain

Proceedings of the National Academy of Sciences of the United States of America
Ke YangPeter E Wright

Abstract

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 α-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...Continue Reading

References

Nov 1, 1995·Journal of Biomolecular NMR·F DelaglioA Bax
Mar 22, 2001·Molecular and Cellular Biology·P ErnstS J Korsmeyer
Mar 17, 2004·Journal of Molecular Biology·Tsaffrir ZorPeter E Wright
Feb 5, 2005·Developmental Cell·Mark L SandbergMichael P Cooke
Feb 24, 2005·American Journal of Hematology·Christophe Nicot
Oct 29, 2005·Journal of Molecular Biology·Roberto N De GuzmanPeter E Wright
Jan 13, 2006·Proceedings of the National Academy of Sciences of the United States of America·Yorifumi SatouMasao Matsuoka
Mar 27, 2007·Nature Reviews. Cancer·Masao Matsuoka, Kuan-Teh Jeang
Aug 21, 2007·Journal of Molecular Biology·Julita A Ramírez, Jennifer K Nyborg
Jun 25, 2008·Nature Reviews. Cancer·Robert G Ramsay, Thomas J Gonda
Feb 11, 2009·Journal of the American Chemical Society·Sven BrüschweilerMartin Tollinger
Aug 1, 2007·Journal of Applied Crystallography·Airlie J McCoyRandy J Read
Oct 14, 2009·Blood·Erin A KimbrelAndrew L Kung
Jan 23, 2010·The Journal of Clinical Investigation·Shenghao JinAlan M Gewirtz
Apr 19, 2011·Journal of Molecular Biology·Pamela R CookIsabelle Lemasson
Sep 1, 1994·Journal of Biomolecular NMR·B A Johnson, R A Blevins
May 9, 2013·ACS Chemical Biology·Sven BrüschweilerMartin Tollinger
Aug 14, 2013·Proceedings of the National Academy of Sciences of the United States of America·Ferruccio PalazzesiMichele Parrinello
Apr 18, 2014·Nature·Hesam N MotlaghVincent J Hilser
Apr 30, 2014·Chemical Reviews·Robin van der LeeM Madan Babu
Jul 9, 2014·Proceedings of the National Academy of Sciences of the United States of America·Sean M LawCharles L Brooks
Jul 23, 2014·Proceedings of the National Academy of Sciences of the United States of America·Ningkun WangAnna K Mapp
Aug 6, 2014·Proceedings of the National Academy of Sciences of the United States of America·Sarah L ShammasJane Clarke
Dec 23, 2014·Nature Reviews. Molecular Cell Biology·Peter E Wright, H Jane Dyson
Jul 22, 2015·Proceedings of the National Academy of Sciences of the United States of America·Munehito AraiPeter E Wright
Mar 1, 2016·Chemical Reviews·Veronika CsizmokJulie D Forman-Kay
Mar 17, 2016·Retrovirology·Guangyong MaMasao Matsuoka
Dec 27, 2016·Experimental Hematology·Sagar UttarkarKarl-Heinz Klempnauer

❮ Previous
Next ❯

Citations

Dec 29, 2020·The Journal of Biological Chemistry·Katrine BuggeKaren Skriver
May 6, 2021·Current Opinion in Structural Biology·H Jane Dyson, Peter E Wright
Nov 14, 2019·Accounts of Chemical Research·Anand DivakaranWilliam C K Pomerantz
Aug 29, 2019·ACS Omega·Denzelle L LyngdohTimir Tripathi
Sep 8, 2021·Journal of the American Chemical Society·Stephen T JoyAnna K Mapp

❮ Previous
Next ❯

Related Concepts

Related Feeds

Alzheimer's Disease: Transcription

Impaired transcription is associated with the pathogenesis and progression of conditions such as Alzheimer's disease (AD). Here are the latest discoveries pertaining to transcription and AD.