5TUA

structure of a Na+-selective mutant of two-pore channel from Arabidopsis thaliana AtTPC1

Summary for 5TUA

• Entry DOI: 10.2210/pdb5tua/pdb
• Descriptor: Two pore calcium channel protein 1, CALCIUM ION, BARIUM ION, ... (4 entities in total)
• Functional Keywords: two-pore channel, na+-selective, metal transport, membrane protein
• Biological source: Arabidopsis thaliana (Mouse-ear cress)
• Total number of polymer chains: 1
• Total formula weight: 86817.50

Authors

Guo, J.,Zeng, W.,Jiang, Y. (deposition date: 2016-11-05, release date: 2017-01-18, Last modification date: 2023-10-04)

Primary citation

Guo, J.,Zeng, W.,Jiang, Y.
Tuning the ion selectivity of two-pore channels.
Proc. Natl. Acad. Sci. U.S.A., 114:1009-1014, 2017

PubMed Abstract: Organellar two-pore channels (TPCs) contain two copies of a Shaker-like six-transmembrane (6-TM) domain in each subunit and are ubiquitously expressed in plants and animals. Interestingly, plant and animal TPCs share high sequence similarity in the filter region, yet exhibit drastically different ion selectivity. Plant TPC1 functions as a nonselective cation channel on the vacuole membrane, whereas mammalian TPC channels have been shown to be endo/lysosomal Na-selective or Ca-release channels. In this study, we performed systematic characterization of the ion selectivity of TPC1 from Arabidopsis thaliana (AtTPC1) and compared its selectivity with the selectivity of human TPC2 (HsTPC2). We demonstrate that AtTPC1 is selective for Ca over Na, but nonselective among monovalent cations (Li, Na, and K). Our results also confirm that HsTPC2 is a Na-selective channel activated by phosphatidylinositol 3,5-bisphosphate. Guided by our recent structure of AtTPC1, we converted AtTPC1 to a Na-selective channel by mimicking the selectivity filter of HsTPC2 and identified key residues in the TPC filters that differentiate the selectivity between AtTPC1 and HsTPC2. Furthermore, the structure of the Na-selective AtTPC1 mutant elucidates the structural basis for Na selectivity in mammalian TPCs.

PubMed: 28096396
DOI: 10.1073/pnas.1616191114

Experimental method

X-RAY DIFFRACTION (3.3 Å)