Structural Insights into KCTD Protein Assembly and Cullin3 Recognition

Journal of Molecular Biology
Alan X JiGilbert G Privé

Abstract

Cullin3 (Cul3)-based ubiquitin E3 ligase complexes catalyze the transfer of ubiquitin from an E2 enzyme to target substrate proteins. In these assemblies, the C-terminal region of Cul3 binds Rbx1/E2-ubiquitin, while the N-terminal region interacts with various BTB (bric-à-brac, tramtrack, broad complex) domain proteins that serve as substrate adaptors. Previous crystal structures of the homodimeric BTB proteins KLHL3, KLHL11 and SPOP in complex with the N-terminal domain of Cul3 revealed the features required for Cul3 recognition in these proteins. A second class of BTB-domain-containing proteins, the KCTD proteins, is also Cul3 substrate adaptors, but these do not share many of the previously identified determinants for Cul3 binding. We report the pentameric crystal structures of the KCTD1 and KCTD9 BTB domains and identify plasticity in the KCTD1 rings. We find that the KCTD proteins 5, 6, 9 and 17 bind to Cul3 with high affinity, while the KCTD proteins 1 and 16 do not have detectable binding. Finally, we confirm the 5:5 assembly of KCTD9/Cul3 complexes by cryo-electron microscopy and provide a molecular rationale for BTB-mediated Cul3 binding specificity in the KCTD family.

References

Jul 1, 1997·The EMBO Journal·H AberleR Kemler
Jun 5, 2003·Journal of Structural Biology·Joseph A Mindell, Nikolaus Grigorieff
Oct 7, 2003·Nature Cell Biology·Manabu FurukawaYue Xiong
Oct 8, 2003·Systematic Biology·Stéphane Guindon, Olivier Gascuel
Mar 23, 2004·Nucleic Acids Research·Robert C Edgar
Jul 14, 2004·Proceedings of the National Academy of Sciences of the United States of America·Lucia Di MarcotullioAlberto Gulino
Dec 2, 2004·Acta Crystallographica. Section D, Biological Crystallography·E Krissinel, K Henrick
Oct 7, 2005·Genome Biology·Peter J StogiosGilbert G Privé
Mar 3, 2006·Acta Crystallographica. Section D, Biological Crystallography·Hideyuki MiyatakeAkihito Yamano
Aug 8, 2007·Journal of Molecular Biology·Evgeny Krissinel, Kim Henrick
Dec 7, 2007·Journal of Huazhong University of Science and Technology. Medical Sciences = Hua Zhong Ke Ji Da Xue Xue Bao. Yi Xue Ying De Wen Ban = Huazhong Keji Daxue Xuebao. Yixue Yingdewen Ban·Jiaquan HuangQin Ning
Jan 25, 2008·BMC Bioinformatics·Yang Zhang
Jun 25, 2008·The FEBS Journal·Yolanda BayónAndrés Alonso
Apr 14, 2009·Journal of Molecular Biology·Irina S DementievaSteve A N Goldstein
Dec 9, 2009·Biochemical and Biophysical Research Communications·Hyder Usman, M K Mathew
Feb 4, 2010·Acta Crystallographica. Section D, Biological Crystallography·Paul D AdamsPeter H Zwart
Jan 18, 2011·Biochimie·Stefania CorrealeEmilia Maria Pedone
Jun 28, 2011·Nature Methods·Xiaoping YangDavid E Root
Sep 13, 2011·Molecular Cell·Woong KimSteven P Gygi
May 11, 2012·Molecular Biology of the Cell·Stephan LangeJu Chen
May 23, 2012·Annals of Human Genetics·Birgit KrabichlerEdda Haberlandt
May 29, 2012·Structure·Wesley J ErringtonGilbert G Privé
Sep 25, 2012·Journal of Structural Biology·Sjors H W Scheres
Oct 5, 2012·The Journal of Biological Chemistry·Riad SeddikBernhard Bettler
Jan 26, 2013·The Journal of Biological Chemistry·Peter CanningAlex N Bullock
Feb 5, 2013·Clinical Immunology : the Official Journal of the Clinical Immunology Society·Tao ChenQin Ning
Apr 11, 2013·PloS One·Alan X Ji, Gilbert G Privé
Apr 18, 2013·BioEssays : News and Reviews in Molecular, Cellular and Developmental Biology·Mikhail SkoblovAncha Baranova
Nov 26, 2013·Cell & Bioscience·Zhepeng LiuGuihong Sun
Nov 26, 2013·Journal of Structural Biology·Chelsea R MarrJohn L Rubinstein
Jan 8, 2014·Methods in Molecular Biology·Bo SalomonsenBarbara A Halkier

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Citations

Oct 1, 2017·The Biochemical Journal·Daniel M PinkasAlex N Bullock
Apr 12, 2019·Proceedings of the National Academy of Sciences of the United States of America·Hao ZuoQing R Fan
Apr 27, 2019·Frontiers in Immunology·Xiaoping ZhangQin Ning
Jun 15, 2019·CNS Neuroscience & Therapeutics·Xinchen TengJ Marie Hardwick
Oct 30, 2020·International Journal of Molecular Sciences·Jordan BlondelleStephan Lange
May 19, 2021·Cell Communication and Signaling : CCS·Annapaola AngrisaniMarta Moretti
Mar 18, 2020·The Journal of Physical Chemistry. B·Lena SchnarrKlaus Weisz

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