The function of the two-pore channel TPC1 depends on dimerization of its carboxy-terminal helix

Cellular and Molecular Life Sciences : CMLS
Nina LarischPetra Dietrich

Abstract

Two-pore channels (TPCs) constitute a family of intracellular cation channels with diverse permeation properties and functions in animals and plants. In the model plant Arabidopsis, the vacuolar cation channel TPC1 is involved in propagation of calcium waves and in cation homeostasis. Here, we discovered that the dimerization of a predicted helix within the carboxyl-terminus (CTH) is essential for the activity of TPC1. Bimolecular fluorescence complementation and co-immunoprecipitation demonstrated the interaction of the two C-termini and pointed towards the involvement of the CTH in this process. Synthetic CTH peptides dimerized with a dissociation constant of 3.9 µM. Disruption of this domain in TPC1 either by deletion or point mutations impeded the dimerization and cation transport. The homo-dimerization of the CTH was analyzed in silico using coarse-grained molecular dynamics (MD) simulations for the study of aggregation, followed by atomistic MD simulations. The simulations revealed that the helical region of the wild type, but not a mutated CTH forms a highly stable, antiparallel dimer with characteristics of a coiled-coil. We propose that the voltage- and Ca(2+)-sensitive conformation of TPC1 depends on C-terminal dimeri...Continue Reading

References

Mar 5, 1973·Journal of Molecular Biology·P Y Chou, G D Fasman
Jun 1, 1994·Genes & Development·R A RuppH Weintraub
Apr 1, 1997·Proceedings of the National Academy of Sciences of the United States of America·I Marten, T Hoshi
Mar 1, 1985·Physical Review A: General Physics·W G Hoover
Jan 23, 1999·The Journal of Membrane Biology·O R DobrovinskayaI I Pottosin
Feb 13, 2001·FEBS Letters·P W van den WijngaardA H de Boer
May 2, 2001·The Journal of Membrane Biology·I I PottosinJ Muñiz
Sep 29, 2001·Plant & Cell Physiology·T FuruichiS Muto
May 7, 2002·Trends in Plant Science·Mansour KarimiAnn Depicker
Nov 1, 1995·Plant Physiology·X. NiuJ. M. Pardo
Jan 17, 2003·Plant Physiology·Rainer SchwackeReinhard Kunze
Mar 1, 2003·The Plant Journal : for Cell and Molecular Biology·Olivier VoinnetDavid Baulcombe
Jun 26, 2003·Nucleic Acids Research·John C ObenauerMichael B Yaffe
Nov 9, 2004·Bioinformatics·Johannes Söding
Dec 14, 2004·The Journal of Biological Chemistry·Bernd NiliusMichael X Zhu
Dec 18, 2004·Planta·Igor I PottosinGerald Schönknecht
Feb 3, 2005·The Plant Journal : for Cell and Molecular Biology·Natalya Ivashikina, Rainer Hedrich
May 10, 2005·The Journal of Physiology·Bernd NiliusThomas Voets
Jun 28, 2005·Nucleic Acids Research·Johannes SödingAndrei N Lupas
Jan 11, 2007·The Journal of Chemical Physics·Giovanni BussiMichele Parrinello
Jan 27, 2007·The Plant Journal : for Cell and Molecular Biology·Gustavo BonaventureEdward E Farmer
Mar 16, 2007·Journal of Experimental Botany·I I Pottosin, G Schönknecht
Sep 4, 2007·The Plant Journal : for Cell and Molecular Biology·A LatzR Hedrich
Nov 22, 2007·The Plant Journal : for Cell and Molecular Biology·Stefanie RanfPetra Dietrich
Dec 7, 2007·Experimental & Molecular Medicine·Eun Hui Lee, Paul D Allen
Jan 25, 2008·BMC Bioinformatics·Yang Zhang
Dec 19, 2008·The Biochemical Journal·G Cristina BrailoiuNae J Dun
Feb 28, 2009·Nature Protocols·Lawrence A Kelley, Michael J E Sternberg
Mar 21, 2009·The Plant Journal : for Cell and Molecular Biology·Diana BeyhlRainer Hedrich
Mar 24, 2009·FEBS Letters·Igor PottosinSergey Shabala
Apr 24, 2009·Nature·Peter J CalcraftMichael X Zhu
Jun 27, 2009·Pflügers Archiv : European journal of physiology·Xiangang ZongChristian Wahl-Schott
Jan 12, 2010·Plant & Cell Physiology·Mohammad Mahbub IslamYoshiyuki Murata
Apr 22, 2010·Proteins·Kresten Lindorff-LarsenDavid E Shaw
Jun 16, 2010·PLoS Computational Biology·Semen O YesylevskyySiewert J Marrink
Aug 20, 2010·The Journal of Biological Chemistry·Samantha J PittRebecca Sitsapesan
Oct 1, 2010·The Journal of Biological Chemistry·Eugen BrailoiuSandip Patel
Nov 5, 2010·Cold Spring Harbor Perspectives in Biology·Antony Galione

❮ Previous
Next ❯

Citations

Jul 22, 2016·Channels·Sandra Feijóo-BandínFrancisca Lago
Nov 9, 2016·Frontiers in Physiology·Stefan Gahbauer, Rainer A Böckmann
Jun 29, 2017·The FEBS Journal·Alexander F Kintzer, Robert M Stroud
May 1, 2018·Cellular and Molecular Life Sciences : CMLS·Sonja A KirschPetra Dietrich
Sep 8, 2018·Proceedings of the National Academy of Sciences of the United States of America·Alexander F KintzerRobert M Stroud
Dec 15, 2016·Frontiers in Plant Science·Moez HaninKhaled Masmoudi
Jan 1, 2018·Functional Plant Biology : FPB·Igor Pottosin, Oxana Dobrovinskaya
Mar 24, 2020·The Journal of Physical Chemistry. B·Stefan Gahbauer, Rainer A Böckmann

❮ Previous
Next ❯

Methods Mentioned

BETA
amino acid exchange
Co-IP
PCR
confocal microscopy
transfection
immunoprecipitation
protein assay
co-immunoprecipitation
fluorescence microscopy
microscale thermophoresis

Software Mentioned

Leica Confocal Software
martinize
DAFT
MARTINI
PULSE
PyMOL

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.

© 2022 Meta ULC. All rights reserved