An isolated CLASP TOG domain suppresses microtubule catastrophe and promotes rescue

Molecular Biology of the Cell
Shreoshi MajumdarLuke M Rice

Abstract

Microtubules are heavily regulated dynamic polymers of αβ-tubulin that are required for proper chromosome segregation and organization of the cytoplasm. Polymerases in the XMAP215 family use arrayed TOG domains to promote faster microtubule elongation. Regulatory factors in the cytoplasmic linker associated protein (CLASP) family that reduce catastrophe and/or increase rescue also contain arrayed TOGs, but how CLASP TOGs contribute to activity is poorly understood. Here, using Saccharomyces cerevisiae Stu1 as a model CLASP, we report structural, biochemical, and reconstitution studies that clarify functional properties of CLASP TOGs. The two TOGs in Stu1 have very different tubulin-binding properties: TOG2 binds to both unpolymerized and polymerized tubulin, and TOG1 binds very weakly to either. The structure of Stu1-TOG2 reveals a CLASP-specific residue that likely confers distinctive tubulin-binding properties. The isolated TOG2 domain strongly suppresses microtubule catastrophe and increases microtubule rescue in vitro, contradicting the expectation that regulatory activity requires an array of TOGs. Single point mutations on the tubulin-binding surface of TOG2 ablate its anti-catastrophe and rescue activity in vitro, and St...Continue Reading

References

Dec 17, 1997·Molecular Biology of the Cell·K SchwartzD Botstein
Aug 31, 2000·Journal of Molecular Biology·C NotredameJ Heringa
Oct 25, 2000·Methods in Enzymology·B A GriffinR Y Tsien
Jul 21, 2004·Journal of Computational Chemistry·Eric F PettersenThomas E Ferrin
Jan 6, 2005·The Journal of Cell Biology·Yuko Mimori-KiyosueAnna Akhmanova
Jul 21, 2006·Acta Crystallographica. Section D, Biological Crystallography·Wladek MinorMaksymilian Chruszcz
Nov 23, 2006·Current Biology : CB·Ksenija DrabekNiels Galjart
Sep 25, 2007·Molecular Cell·Kevin C Slep, Ronald D Vale
Dec 7, 2007·Nature·Peter BielingThomas Surrey
Dec 7, 2007·Developmental Cell·Scott V Bratman, Fred Chang
Jul 28, 2009·Cell·Srinivas HonnappaMichel O Steinmetz
Sep 17, 2009·Biochemical Society Transactions·Kevin C Slep
Oct 24, 2009·PloS One·Marija ZanicJonathon Howard
Nov 17, 2009·Nature Methods·Kohei NishimuraMasato Kanemaki
Dec 3, 2009·Genes & Development·Jennifer OrtizJohannes Lechner
Jan 9, 2010·Acta Crystallographica. Section D, Biological Crystallography·Vincent B ChenDavid C Richardson
Feb 4, 2010·Acta Crystallographica. Section D, Biological Crystallography·Paul D AdamsPeter H Zwart
Apr 13, 2010·Acta Crystallographica. Section D, Biological Crystallography·P EmsleyK Cowtan
May 6, 2010·Biophysical Journal·Peter Schuck
May 15, 2010·Methods in Cell Biology·Christopher GellJonathon Howard
Aug 17, 2010·Developmental Cell·Jawdat Al-BassamFred Chang
Feb 2, 2011·Proceedings of the National Academy of Sciences of the United States of America·Per O WidlundJonathon Howard
Jul 26, 2011·Trends in Cell Biology·Jawdat Al-Bassam, Fred Chang
Aug 30, 2012·Nature Methods·Caroline A SchneiderKevin W Eliceiri
Feb 11, 2014·Current Biology : CB·Sebastian P MaurerThomas Surrey
May 28, 2014·The Journal of Cell Biology·Caroline FunkJohannes Lechner
Jun 27, 2014·Molecular Biology of the Cell·Jaime C FoxKevin C Slep
May 25, 2015·Journal of Molecular Biology·Takahisa MakiIkuko Hayashi
Sep 18, 2015·Molecular Biology of the Cell·Alakananda DasKevin C Slep
Nov 13, 2015·Nature Reviews. Molecular Cell Biology·Anna Akhmanova, Michel O Steinmetz
Jan 8, 2016·Analytical Biochemistry·Thomas H ScheuermannChad A Brautigam

❮ Previous
Next ❯

Citations

Nov 1, 2018·The Journal of Cell Biology·Jelmer J LindeboomDavid W Ehrhardt
Jul 20, 2019·PloS One·Jonathan B Leano, Kevin C Slep
Feb 23, 2020·Protein Science : a Publication of the Protein Society·Xuecheng YeLuke M Rice
Aug 21, 2020·Proceedings of the National Academy of Sciences of the United States of America·Pavel FilipčíkPeter D Mace
Apr 26, 2020·Journal of Cell Science·Elizabeth J LawrenceLuke M Rice
Nov 24, 2019·The Journal of Cell Biology·Hugo GirãoHelder Maiato
Nov 8, 2020·Current Opinion in Cell Biology·Ryoma OhiMarija Zanic
Jun 5, 2021·Nature Chemical Biology·Nandini ManiRadhika Subramanian
Jun 10, 2020·Current Biology : CB·Kevin C Slep
Aug 20, 2021·Nature Reviews. Molecular Cell Biology·Nikita B Gudimchuk, J Richard McIntosh

❮ Previous
Next ❯

Methods Mentioned

BETA
GTPase
gel filtration
fluorescence microscopy
microscale thermophoresis
x-ray crystallography
x-ray scattering
PCR

Software Mentioned

DAMMIF
GraphPad Prism
Chimera
GNOM
MolProbity
Manager
MATLAB
HKL3000
ImageJ
SEDNTERP

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.