@article{MTMT:30637149,
	title = {Enzyme activity and selectivity filter stability of ancient TRPM2 channels were simultaneously lost in early vertebrates},
	url = {https://m2.mtmt.hu/api/publication/30637149},
	author = {Iordanov, Iordan and Tóth, Balázs and Szöllősi, András and Csanády, László},
	doi = {10.7554/eLife.44556},
	journal-iso = {ELIFE},
	journal = {ELIFE},
	volume = {8},
	unique-id = {30637149},
	issn = {2050-084X},
	abstract = {Transient Receptor Potential Melastatin 2 (TRPM2) is a cation channel important for the immune response, insulin secretion, and body temperature regulation. It is activated by cytosolic ADP ribose (ADPR) and contains a nudix-type motif 9 (NUDT9)-homology (NUDT9-H) domain homologous to ADPR phosphohydrolases (ADPRases). Human TRPM2 (hsTRPM2) is catalytically inactive due to mutations in the conserved Nudix box sequence. Here, we show that TRPM2 Nudix motifs are canonical in all invertebrates but vestigial in vertebrates. Correspondingly, TRPM2 of the cnidarian Nematostella vectensis (nvTRPM2) and the choanoflagellate Salpingoeca rosetta (srTRPM2) are active ADPRases. Disruption of ADPRase activity fails to affect nvTRPM2 channel currents, reporting a catalytic cycle uncoupled from gating. Furthermore, pore sequence substitutions responsible for inactivation of hsTRPM2 also appeared in vertebrates. Correspondingly, zebrafish (Danio rerio) TRPM2 (drTRPM2) and hsTRPM2 channels inactivate, but srTRPM2 and nvTRPM2 currents are stable. Thus, catalysis and pore stability were lost simultaneously in vertebrate TRPM2 channels.},
	keywords = {Xenopus; E. coli; molecular biophysics; Structural biology; Selectivity filter; ADP ribose; Nudix hydrolase; channel enzyme; rundown},
	year = {2019},
	eissn = {2050-084X},
	orcid-numbers = {Iordanov, Iordan/0000-0001-8251-5857; Tóth, Balázs/0000-0002-1257-2597; Szöllősi, András/0000-0002-5570-4609; Csanády, László/0000-0002-6547-5889}
}

@article{MTMT:3210856,
	title = {Molecular Structure of the Human CFTR Ion Channel},
	url = {https://m2.mtmt.hu/api/publication/3210856},
	author = {Liu, F and Zhang, Z and Csanády, László and Gadsby, DC and Chen, J},
	doi = {10.1016/j.cell.2017.02.024},
	journal-iso = {CELL},
	journal = {CELL},
	volume = {169},
	unique-id = {3210856},
	issn = {0092-8674},
	abstract = {The cystic fibrosis transmembrane conductance regulator (CFTR) is an ATP-binding cassette (ABC) transporter that uniquely functions as an ion channel. Here, we present a 3.9 Å structure of dephosphorylated human CFTR without nucleotides, determined by electron cryomicroscopy (cryo-EM). Close resemblance of this human CFTR structure to zebrafish CFTR under identical conditions reinforces its relevance for understanding CFTR function. The human CFTR structure reveals a previously unresolved helix belonging to the R domain docked inside the intracellular vestibule, precluding channel opening. By analyzing the sigmoid time course of CFTR current activation, we propose that PKA phosphorylation of the R domain is enabled by its infrequent spontaneous disengagement, which also explains residual ATPase and gating activity of dephosphorylated CFTR. From comparison with MRP1, a feature distinguishing CFTR from all other ABC transporters is the helix-loop transition in transmembrane helix 8, which likely forms the structural basis for CFTR's channel function. © 2017 Elsevier Inc.},
	keywords = {ABC transporter; anion channel; human CFTR; cryo-EM},
	year = {2017},
	eissn = {1097-4172},
	pages = {85-95.e8},
	orcid-numbers = {Csanády, László/0000-0002-6547-5889}
}

@article{MTMT:2333381,
	title = {Conformational changes in the catalytically inactive nucleotide-binding site of CFTR},
	url = {https://m2.mtmt.hu/api/publication/2333381},
	author = {Csanády, László and Mihályi, Csaba and Szöllősi, András and Törőcsik, Beáta and Vergani, P},
	doi = {10.1085/jgp.201210954},
	journal-iso = {J GEN PHYSIOL},
	journal = {JOURNAL OF GENERAL PHYSIOLOGY},
	volume = {142},
	unique-id = {2333381},
	issn = {0022-1295},
	abstract = {A central step in the gating of the cystic fibrosis transmembrane conductance regulator (CFTR) chloride channel is the association of its two cytosolic nucleotide-binding domains (NBDs) into a head-to-tail dimer, with two nucleotides bound at the interface. Channel opening and closing, respectively, are coupled to formation and disruption of this tight NBD dimer. CFTR is an asymmetric adenosine triphosphate (ATP)-binding cassette protein in which the two interfacial-binding sites (composite sites 1 and 2) are functionally different. During gating, the canonical, catalytically active nucleotide-binding site (site 2) cycles between dimerized prehydrolytic (state O1), dimerized post-hydrolytic (state O2), and dissociated (state C) forms in a preferential C-->O1-->O2-->C sequence. In contrast, the catalytically inactive nucleotide-binding site (site 1) is believed to remain associated, ATP-bound, for several gating cycles. Here, we have examined the possibility of conformational changes in site 1 during gating, by studying gating effects of perturbations in site 1.Previous work showed that channel closure is slowed, both under hydrolytic and nonhydrolytic conditions, by occupancy of site 1 by N6-(2-phenylethyl)-ATP (P-ATP) as well as by the site-1 mutation H1348A (NBD2 signature sequence). Here, we found that P-ATP prolongs wild-type (WT) CFTR burst durations by selectively slowing (>2x) transition O1-->O2 and decreases the nonhydrolytic closing rate (transition O1-->C) of CFTR mutants K1250A ( approximately 4x) and E1371S ( approximately 3x). Mutation H1348A also slowed ( approximately 3x) the O1-->O2 transition in the WT background and decreased the nonhydrolytic closing rate of both K1250A ( approximately 3x) and E1371S ( approximately 3x) background mutants. Neither P-ATP nor the H1348A mutation affected the 1:1 stoichiometry between ATP occlusion and channel burst events characteristic to WT CFTR gating in ATP. The marked effect that different structural perturbations at site 1 have on both steps O1-->C and O1-->O2 suggests that the overall conformational changes that CFTR undergoes upon opening and coincident with hydrolysis at the active site 2 include significant structural rearrangement at site 1.},
	year = {2013},
	eissn = {1540-7748},
	pages = {61-73},
	orcid-numbers = {Csanády, László/0000-0002-6547-5889; Mihályi, Csaba/0000-0001-7536-3066; Szöllősi, András/0000-0002-5570-4609; Törőcsik, Beáta/0000-0002-9838-3710}
}

@article{MTMT:1493089,
	title = {Preferential phosphorylation of R-domain serine 768 dampens activation of CFTR channels by PKA},
	url = {https://m2.mtmt.hu/api/publication/1493089},
	author = {Csanády, László and Seto-Young, D and Chan, KW and Cenciarelli, C and Angel, BB and Qin, J and McLachlin, DT and Krutchinsky, AN and Chait, BT and Nairn, AC and Gadsby, DC},
	doi = {10.1085/jgp.200409076},
	journal-iso = {J GEN PHYSIOL},
	journal = {JOURNAL OF GENERAL PHYSIOLOGY},
	volume = {125},
	unique-id = {1493089},
	issn = {0022-1295},
	year = {2005},
	eissn = {1540-7748},
	pages = {171-186},
	orcid-numbers = {Csanády, László/0000-0002-6547-5889}
}

@article{MTMT:1493091,
	title = {Severed molecules functionally define the boundaries of the cystic fibrosis transmembrane conductance regulator's NH2-terminal nucleotide binding domain},
	url = {https://m2.mtmt.hu/api/publication/1493091},
	author = {Chan, KW and Csanády, László and Seto-Young, D and Nairn, AC and Gadsby, DC},
	doi = {10.1085/jgp.116.2.163},
	journal-iso = {J GEN PHYSIOL},
	journal = {JOURNAL OF GENERAL PHYSIOLOGY},
	volume = {116},
	unique-id = {1493091},
	issn = {0022-1295},
	year = {2000},
	eissn = {1540-7748},
	pages = {163-180},
	orcid-numbers = {Csanády, László/0000-0002-6547-5889}
}

@article{MTMT:1493767,
	title = {Severed channels probe regulation of gating of cystic fibrosis transmembrane conductance regulator by its cytoplasmic domains},
	url = {https://m2.mtmt.hu/api/publication/1493767},
	author = {Csanády, László and Chan, KW and Seto-Young, D and Kopsco, DC and Nairn, AC and Gadsby, DC},
	doi = {10.1085/jgp.116.3.477},
	journal-iso = {J GEN PHYSIOL},
	journal = {JOURNAL OF GENERAL PHYSIOLOGY},
	volume = {116},
	unique-id = {1493767},
	issn = {0022-1295},
	year = {2000},
	eissn = {1540-7748},
	pages = {477-500},
	orcid-numbers = {Csanády, László/0000-0002-6547-5889}
}