Two Tau binding sites on tubulin revealed by thiol-disulfide exchanges

Scientific Reports
Marlène MartinhoPascale Barbier

Abstract

Tau is a Microtubule-associated protein that induces and stabilizes the formation of the Microtubule cytoskeleton and plays an important role in neurodegenerative diseases. The Microtubules binding region of Tau has been determined for a long time but where and how Tau binds to its partner still remain a topic of debate. We used Site Directed Spin Labeling combined with EPR spectroscopy to monitor Tau upon binding to either Taxol-stabilized MTs or to αβ-tubulin when Tau is directly used as an inducer of MTs formation. Using maleimide-functionalized labels grafted on the two natural cysteine residues of Tau, we found in both cases that Tau remains highly flexible in these regions confirming the fuzziness of Tau:MTs complexes. More interestingly, using labels linked by a disulfide bridge, we evidenced for the first time thiol disulfide exchanges between αβ-tubulin or MTs and Tau. Additionally, Tau fragments having the two natural cysteines or variants containing only one of them were used to determine the role of each cysteine individually. The difference observed in the label release kinetics between preformed MTs or Tau-induced MTs, associated to a comparison of structural data, led us to propose two putative binding sites of T...Continue Reading

References

May 1, 1975·Proceedings of the National Academy of Sciences of the United States of America·M D WeingartenM W Kirschner
Jan 1, 1991·Pharmacology & Therapeutics·R F Luduena, M C Roach
Nov 1, 1991·The Journal of Cell Biology·K A Butner, M W Kirschner
Nov 8, 1986·Lancet·J P BrionP Dustin
Nov 15, 1984·Nature·T Mitchison, M Kirschner
May 1, 1995·Neurobiology of Aging·E M MandelkowE Mandelkow
Aug 29, 1995·Proceedings of the National Academy of Sciences of the United States of America·O SchweersE Mandelkow
Jul 19, 2000·Biochimica Et Biophysica Acta·P FriedhoffE Mandelkow
Feb 13, 2001·Current Opinion in Cell Biology·M L Garcia, D W Cleveland
Jul 5, 2001·Biochemical and Biophysical Research Communications·K BhattacharyaS K Sharma
Jul 10, 2001·Annual Review of Biophysics and Biomolecular Structure·E Nogales
Aug 25, 2001·Annual Review of Neuroscience·V M LeeJ Q Trojanowski
May 23, 2002·The Journal of Biological Chemistry·P J BrittoJ Wolff
Jun 26, 2002·The Journal of Cell Biology·Jawdat Al-BassamRonald A Milligan
Dec 31, 2002·The EMBO Journal·Santwana KarLinda A Amos
Jul 30, 2003·Proceedings of the National Academy of Sciences of the United States of America·Dulal PandaLeslie Wilson
Apr 21, 2004·Proceedings of the National Academy of Sciences of the United States of America·Victoria MakridesJohn Lew
May 19, 2004·Journal of Molecular Biology·Rachel A SantarellaAndreas Hoenger
Jun 26, 2004·Chemistry & Biology·Linda A Amos
Jul 29, 2004·Organic & Biomolecular Chemistry·Linda A Amos
Sep 29, 2005·Journal of Magnetic Resonance·Stefan Stoll, Arthur Schweiger
Feb 20, 2007·The Journal of Biological Chemistry·Marco D MukraschMarkus Zweckstetter
Dec 7, 2007·Trends in Biochemical Sciences·Peter Tompa, Monika Fuxreiter
Dec 19, 2007·Methods in Molecular Medicine·José Manuel Andreu
Aug 10, 2011·Topics in Current Chemistry·Malte Drescher
Apr 30, 2013·Nature Structural & Molecular Biology·Todd J CohenVirginia M Y Lee
Oct 25, 2013·Nucleic Acids Research·Tjaart A P de BeerRoman A Laskowski
Aug 28, 2014·Journal of the American Chemical Society·Benoît GigantGuy Lippens
Sep 10, 2014·International Journal of Molecular Sciences·Isabelle L Di MaïoVincent Peyrot
Jun 3, 2015·Proceedings of the National Academy of Sciences of the United States of America·Harindranath KadavathMarkus Zweckstetter

❮ Previous
Next ❯

Citations

Aug 27, 2019·Frontiers in Aging Neuroscience·Pascale BarbierIsabelle Landrieu
Mar 24, 2020·Science Advances·S WeickertM Drescher
Jul 4, 2019·The Journal of Biological Chemistry·Rebecca L BestStuart C Feinstein
Mar 3, 2019·Acta Neuropathologica Communications·Yann FichouIsabelle Landrieu
Apr 18, 2019·The Journal of Biological Chemistry·Rabab A CharafeddineTorsten Wittmann
Jan 30, 2020·Structure·Ho Yee Joyce FungElizabeth Rhoades

❮ Previous
Next ❯

Methods Mentioned

BETA
NMR
Fluorescence
exchange ion chromatography
ion-exchange chromatography
electrophoresis
gel filtration

Software Mentioned

EasySpin toolbox
YASARA
SimLabel
MATLAB Graphical User Interface ( GUI )
YASARA View

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.