Phosphatidylinositol-3,5-bisphosphate lipid-binding-induced activation of the human two-pore channel 2

Journal article
(Original article)


Publication Details

Author(s): Kirsch S, Kugemann A, Carpaneto A, Böckmann R, Dietrich P
Journal: Cellular and Molecular Life Sciences
Publisher: SPRINGER BASEL AG
Publication year: 2018
Volume: 75
Journal issue: 20
Pages range: 3803-3815
ISSN: 1420-682X
Language: English


Abstract

Mammalian two-pore channels (TPCs) are activated by the low-abundance membrane lipid phosphatidyl-(3,5)-bisphosphate (PI(3,5)P-2) present in the endo-lysosomal system. Malfunction of human TPC1 or TPC2 (hTPC) results in severe organellar storage diseases and membrane trafficking defects. Here, we compared the lipid-binding characteristics of hTPC2 and of the PI(3,5)P-2-insensitive TPC1 from the model plant Arabidopsis thaliana. Combination of simulations with functional analysis of channel mutants revealed the presence of an hTPC2-specific lipid-binding pocket mutually formed by two channel regions exposed to the cytosolic side of the membrane. We showed that PI(3,5)P-2 is simultaneously stabilized by positively charged amino acids (K203, K204, and K207) in the linker between transmembrane helices S4 and S5 and by S322 in the cytosolic extension of S6. We suggest that PI(3,5)P-2 cross links two parts of the channel, enabling their coordinated movement during channel gating.


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
Kugemann, Andreas
Professur für Zellbiologie der Pflanzen


How to cite

APA:
Kirsch, S., Kugemann, A., Carpaneto, A., Böckmann, R., & Dietrich, P. (2018). Phosphatidylinositol-3,5-bisphosphate lipid-binding-induced activation of the human two-pore channel 2. Cellular and Molecular Life Sciences, 75(20), 3803-3815. https://dx.doi.org/10.1007/s00018-018-2829-5

MLA:
Kirsch, Sonja, et al. "Phosphatidylinositol-3,5-bisphosphate lipid-binding-induced activation of the human two-pore channel 2." Cellular and Molecular Life Sciences 75.20 (2018): 3803-3815.

BibTeX: 

Last updated on 2019-16-01 at 12:10