The crystal structure of the N-terminal region of BUB1 provides insight into the mechanism of BUB1 recruitment to kinetochores.

Structure
Victor M Bolanos-GarciaTom L Blundell

Abstract

The interaction of the central mitotic checkpoint component BUB1 with the mitotic kinetochore protein Blinkin is required for the kinetochore localization and function of BUB1 in the mitotic spindle assembly checkpoint, the regulatory mechanism of the cell cycle that ensures the even distribution of chromosomes during the transition from metaphase to anaphase. Here, we report the 1.74 angstroms resolution crystal structure of the N-terminal region of BUB1. The structure is organized as a tandem arrangement of three divergent units of the tetratricopeptide motif. Functional assays in vivo of native and site-specific mutants identify the residues of human BUB1 important for the interaction with Blinkin and define one region of potential therapeutic interest. The structure provides insight into the molecular basis of Blinkin-specific recognition by BUB1 and, on a broader perspective, of the mechanism that mediates kinetochore localization of BUB1 in checkpoint-activated cells.

References

Dec 1, 1994·The Journal of Cell Biology·I Samejima, M Yanagida
Jan 9, 1996·Proceedings of the National Academy of Sciences of the United States of America·S Jones, J M Thornton
Apr 1, 1998·Nature·D P CahillB Vogelstein
Sep 19, 2000·Genes, Chromosomes & Cancer·A GemmaS Kudoh
Dec 2, 2000·Nature Structural Biology·G J GattoJ M Berg
Mar 10, 2001·Nature·A W Murray, D Marks
Jul 17, 2001·EMBO Reports·A TigheS S Taylor
May 10, 2003·Structure·Ewan R G MainLynne Regan
Sep 6, 2003·Current Biology : CB·Hartmut C VodermaierJan-Michael Peters
Dec 9, 2003·Trends in Biochemical Sciences·Luca D D'Andrea, Lynne Regan
Dec 23, 2003·Journal of Molecular Biology·Juan Fernández-RecioRuben Abagyan
Jun 23, 2004·Nature Genetics·Darren J BakerJan M van Deursen
Jul 23, 2004·Molecular Biology of the Cell·Suzanne VigneronThierry Lorca
Dec 4, 2004·The EMBO Journal·Jing YangDavid Barford
Apr 13, 2005·Proceedings of the National Academy of Sciences of the United States of America·Ewan R G MainLynne Regan
May 4, 2005·Trends in Cell Biology·Vincent Vanoosthuyse, Kevin G Hardwick
May 18, 2005·Philosophical Transactions of the Royal Society of London. Series B, Biological Sciences·Yoshinori Watanabe, Tomoya S Kitajima
May 24, 2005·Experimental Cell Research·Loleta HarrisRakesh Goorha
Jun 28, 2005·Nucleic Acids Research·Emidio CapriottiRita Casadio
Oct 1, 2005·Nature Reviews. Cancer·Geert J P L KopsDon W Cleveland
Oct 19, 2005·Current Opinion in Cell Biology·Yoshinori Watanabe
Dec 20, 2005·Current Biology : CB·Sabine VaurJean-Paul Javerzat
Apr 8, 2006·Experimental Cell Research·James DavenportRakesh Goorha
Nov 7, 2006·Trends in Biochemical Sciences·Victor Martin Bolanos-GarciaTom L Blundell
Jan 18, 2007·Proceedings of the National Academy of Sciences of the United States of America·Nicholas A LarsenStephen C Harrison
Mar 21, 2007·Genes & Development·Janet L Burton, Mark J Solomon
Mar 29, 2007·The Journal of Cell Biology·Yekaterina BoyarchukAlexei Arnaoutov
May 20, 2008·Journal of Molecular Biology·S C OnuohaS E Jackson

❮ Previous
Next ❯

Citations

Dec 29, 2011·Frontiers in Bioscience (Landmark Edition)·Yixin Yao, Wei Dai
Nov 26, 2010·Quarterly Reviews of Biophysics·David Barford
Dec 5, 2012·The Journal of Cell Biology·Robin M RickeJan M van Deursen
Apr 10, 2013·The Journal of Cell Biology·Wilco NijenhuisGeert J P L Kops
Mar 29, 2011·Seminars in Cell & Developmental Biology·Soonjoung Kim, Hongtao Yu
Jul 16, 2010·Trends in Biochemical Sciences·Min Zhou, Carol V Robinson
Oct 20, 2009·Trends in Biochemical Sciences·Judith Zich, Kevin G Hardwick
Mar 18, 2016·Open Biology·Olga O Nerusheva, Bungo Akiyoshi
May 13, 2014·American Journal of Medical Genetics. Part C, Seminars in Medical Genetics·Diana Alcantara, Mark O'Driscoll
Apr 24, 2012·Current Biology : CB·Nitobe LondonSue Biggins
Oct 5, 2010·Trends in Biochemical Sciences·Victor M Bolanos-Garcia, Tom L Blundell
Oct 18, 2014·Frontiers in Physiology·Semin Lee, Victor M Bolanos-Garcia
May 23, 2012·Philosophical Transactions. Series A, Mathematical, Physical, and Engineering Sciences·Victor M Bolanos-GarciaTom L Blundell
Nov 16, 2011·Philosophical Transactions of the Royal Society of London. Series B, Biological Sciences·David Barford
Dec 12, 2012·Open Biology·Richard BaylissSharon Yeoh
Sep 1, 2017·International Journal of Molecular Sciences·Zhiyuan Li, Xin Zhang
Mar 12, 2010·The Journal of Biological Chemistry·Sheena D'ArcyVictor M Bolanos-Garcia
Aug 17, 2018·Open Biology·Spyridon T Pachis, Geert J P L Kops
Mar 16, 2021·Animal Cells and Systems·Taekyung Kim, Anton Gartner
May 16, 2021·Proceedings of the National Academy of Sciences of the United States of America·Handong SuFangpu Han
Jun 3, 2021·International Journal of Environmental Research and Public Health·Urbashi BasnetSourav Roy

❮ Previous
Next ❯

Methods Mentioned

BETA
X-ray
circular dichroism
circular
gel filtration
gel-filtration

Software Mentioned

I Mutant
SDM
Dali

Related Concepts

Related Feeds

Cell Checkpoints & Regulators

Cell cycle checkpoints are a series of complex checkpoint mechanisms that detect DNA abnormalities and ensure that DNA replication and repair are complete before cell division. They are primarily regulated by cyclins, cyclin-dependent kinases, and the anaphase-promoting complex/cyclosome. Here is the latest research.