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

Journal article
(Original article)


Publication Details

Author(s): Larisch N, Kirsch S, Schambony A, Studtrucker T, Böckmann R, Dietrich P
Journal: Cellular and molecular life sciences : CMLS
Publication year: 2016
Volume: 73
Journal issue: 13
Pages range: 2565-81
ISSN: 1420-9071
Language: English


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 dimerization, adding an additional layer to the complex regulation of two-pore cation channels.



FAU Authors / FAU Editors

Böckmann, Rainer Prof. Dr.
Professur für Computational Biology
Dietrich, Petra Prof. Dr.
Professur für Zellbiologie der Pflanzen
Kirsch, Sonja
Professur für Computational Biology
Schambony, Alexandra PD Dr.
Lehrstuhl für Entwicklungsbiologie


How to cite

APA:
Larisch, N., Kirsch, S., Schambony, A., Studtrucker, T., Böckmann, R., & Dietrich, P. (2016). The function of the two-pore channel TPC1 depends on dimerization of its carboxy-terminal helix. Cellular and molecular life sciences : CMLS, 73(13), 2565-81. https://dx.doi.org/10.1007/s00018-016-2131-3

MLA:
Larisch, Nina, et al. "The function of the two-pore channel TPC1 depends on dimerization of its carboxy-terminal helix." Cellular and molecular life sciences : CMLS 73.13 (2016): 2565-81.

BibTeX: 

Last updated on 2018-26-07 at 10:10