Crystal structure of the motor domain of the human kinetochore protein CENP-E

Journal of Molecular Biology
I Garcia-SaezF Kozielski

Abstract

The human kinetochore is a highly complex macromolecular structure that connects chromosomes to spindle microtubules (MTs) in order to facilitate accurate chromosome segregation. Centromere-associated protein E (CENP-E), a member of the kinesin superfamily, is an essential component of the kinetochore, since it is required to stabilize the attachment of chromosomes to spindle MTs, to develop tension across aligned chromosomes, to stabilize spindle poles and to satisfy the mitotic checkpoint. Here we report the 2.5A resolution crystal structure of the motor domain and linker region of human CENP-E with MgADP bound in the active site. This structure displays subtle but important differences compared to the structures of human Eg5 and conventional kinesin. Our structure reveals that the CENP-E linker region is in a "docked" position identical to that in the human plus-end directed conventional kinesin. CENP-E has many advantages as a potential anti-mitotic drug target and this crystal structure of human CENP-E will provide a starting point for high throughput virtual screening of potential inhibitors.

References

May 17, 1990·Nature·C M PfarrJ R McIntosh
Nov 1, 1989·Proceedings of the National Academy of Sciences of the United States of America·P H HirelS Blanquet
Jun 1, 1996·Current Opinion in Cell Biology·T J Yen, B T Schaar
Jan 1, 1996·Cell Motility and the Cytoskeleton·D A ThrowerL Wilson
Feb 12, 1998·The Journal of Cell Biology·B T SchaarT J Yen
Jan 24, 1998·Biochemistry·S SackE Mandelkow
Jun 23, 1998·Current Biology : CB·A Grancell, P K Sorger
Aug 15, 1998·Trends in Cell Biology·C L Rieder, E D Salmon
Oct 3, 1998·Acta Crystallographica. Section D, Biological Crystallography·A T BrüngerG L Warren
Mar 25, 1999·Acta Crystallographica. Section D, Biological Crystallography·R M Esnouf
May 13, 1999·Bioinformatics·P GouetF Métoz
Mar 21, 2000·Biochimica Et Biophysica Acta·G Woehlke, M Schliwa
May 1, 2001·The Journal of Biological Chemistry·J TurnerR Sakowicz
Jun 21, 2001·Proceedings of the National Academy of Sciences of the United States of America·H MikiN Hirokawa
May 16, 2002·The Journal of Cell Biology·Tarun M Kapoor, Duane A Compton
Jan 15, 2003·Biochemistry·Salvatore DeBonisFrank Kozielski
Apr 11, 2003·Molecular Biology of the Cell·Song-Tao LiuTim J Yen
Jul 25, 2003·Cancer Biology & Therapy·S A JablonskiT J Yen
Dec 6, 2003·Journal of Cell Science·Elise M Dagenbach, Sharyn A Endow
Sep 1, 1994·Acta Crystallographica. Section D, Biological Crystallography·UNKNOWN Collaborative Computational Project, Number 4
Jan 1, 1997·Methods in Enzymology·Zbyszek Otwinowski, Wladek Minor
Jan 1, 1997·Methods in Enzymology·Jorge Navaza, Pedro Saludjian

❮ Previous
Next ❯

Citations

Jun 7, 2013·Interdisciplinary Sciences, Computational Life Sciences·Ambuj KumarRituraj Purohit
Jan 26, 2007·Nature Reviews. Cancer·Jeffrey R JacksonPearl S Huang
Jul 25, 2012·Nature Reviews. Cancer·Oliver Rath, Frank Kozielski
Apr 23, 2008·Proceedings of the National Academy of Sciences of the United States of America·Hasan YardimciPaul R Selvin
Sep 18, 2009·The Journal of Biological Chemistry·Steven S RosenfeldJun Xing
Feb 20, 2010·Proceedings of the National Academy of Sciences of the United States of America·Kenneth W WoodJeffrey R Jackson
Sep 8, 2005·The Journal of Cell Biology·Yinghui MaoDon W Cleveland
Feb 19, 2008·Trends in Cell Biology·Masahide Kikkawa
Jul 31, 2013·Journal of Molecular Biology·Vivek MusinipallyEva Nogales
Jun 3, 2008·Journal of Structural Biology·Maia V VinogradovaRobert J Fletterick
Apr 15, 2016·Expert Opinion on Drug Discovery·D DubeP Kaur
Feb 13, 2016·Chemical Biology & Drug Design·Wei ZhangYonghe Li
Apr 30, 2020·Essays in Biochemistry·Benjamin Craske, Julie P I Welburn
Feb 22, 2017·Biology·Helder MaiatoMarin Barisic
Nov 24, 2011·The Journal of Biological Chemistry·Yuejia HuangXuebiao Yao
May 10, 2013·The Journal of Biological Chemistry·Hung Yi Kristal KaanSteven S Rosenfeld
Mar 2, 2021·Acta Crystallographica. Section D, Structural Biology·Asuka ShibuyaHideshi Yokoyama
Sep 19, 2019·Biochemical and Biophysical Research Communications·Masayoshi YamaneAkira Asai
Dec 24, 2018·G3 : Genes - Genomes - Genetics·Amy Huei-Yi LeeDavid S Guttman
Jan 5, 2011·The Journal of Physical Chemistry. B·Wei Zhang

❮ Previous
Next ❯

Related Concepts

Trending Feeds

COVID-19

Coronaviruses encompass a large family of viruses that cause the common cold as well as more serious diseases, such as the ongoing outbreak of coronavirus disease 2019 (COVID-19; formally known as 2019-nCoV). Coronaviruses can spread from animals to humans; symptoms include fever, cough, shortness of breath, and breathing difficulties; in more severe cases, infection can lead to death. This feed covers recent research on COVID-19.

Blastomycosis

Blastomycosis fungal infections spread through inhaling Blastomyces dermatitidis spores. Discover the latest research on blastomycosis fungal infections here.

Nuclear Pore Complex in ALS/FTD

Alterations in nucleocytoplasmic transport, controlled by the nuclear pore complex, may be involved in the pathomechanism underlying multiple neurodegenerative diseases including Amyotrophic Lateral Sclerosis and Frontotemporal Dementia. Here is the latest research on the nuclear pore complex in ALS and FTD.

Applications of Molecular Barcoding

The concept of molecular barcoding is that each original DNA or RNA molecule is attached to a unique sequence barcode. Sequence reads having different barcodes represent different original molecules, while sequence reads having the same barcode are results of PCR duplication from one original molecule. Discover the latest research on molecular barcoding here.

Chronic Fatigue Syndrome

Chronic fatigue syndrome is a disease characterized by unexplained disabling fatigue; the pathology of which is incompletely understood. Discover the latest research on chronic fatigue syndrome here.

Evolution of Pluripotency

Pluripotency refers to the ability of a cell to develop into three primary germ cell layers of the embryo. This feed focuses on the mechanisms that underlie the evolution of pluripotency. Here is the latest research.

Position Effect Variegation

Position Effect Variagation occurs when a gene is inactivated due to its positioning near heterochromatic regions within a chromosome. Discover the latest research on Position Effect Variagation here.

STING Receptor Agonists

Stimulator of IFN genes (STING) are a group of transmembrane proteins that are involved in the induction of type I interferon that is important in the innate immune response. The stimulation of STING has been an active area of research in the treatment of cancer and infectious diseases. Here is the latest research on STING receptor agonists.

Microbicide

Microbicides are products that can be applied to vaginal or rectal mucosal surfaces with the goal of preventing, or at least significantly reducing, the transmission of sexually transmitted infections. Here is the latest research on microbicides.