dc.contributor.author | Chi, Gamma | |
dc.contributor.author | Ebenhoch, Rebecca | |
dc.contributor.author | Man, Henry | |
dc.contributor.author | Tang, Haiping | |
dc.contributor.author | Tremblay, Laurence | |
dc.contributor.author | Reggiano, Gabriella | |
dc.contributor.author | Qiu, Xingyu | |
dc.contributor.author | Bohstedt, Tina | |
dc.contributor.author | Liko, Idlir | |
dc.contributor.author | Almeida, Fernando G. | |
dc.contributor.author | Garneau, Alexandre | |
dc.contributor.author | Wang, Dong | |
dc.contributor.author | McKinley, Gavin | |
dc.contributor.author | Moreau, Christophe P. | |
dc.contributor.author | Bountra, Kiran D. | |
dc.contributor.author | Abrusci, Patrizia | |
dc.contributor.author | Mukhopadhyay, Shubhashish M. M. | |
dc.contributor.author | Fernandez-Cid, Alejandra | |
dc.contributor.author | Slimani, Samira | |
dc.contributor.author | Lavoie, Julie | |
dc.contributor.author | Burgess-Brown, Nicola A. | |
dc.contributor.author | Tehan, Ben | |
dc.contributor.author | DiMaio, Frank | |
dc.contributor.author | Jazayeri, Ali | |
dc.contributor.author | Isenring, Paul | |
dc.contributor.author | Robinson, Carol V. | |
dc.contributor.author | Durr, Katharina L. | |
dc.date.accessioned | 2022-10-31T13:33:52Z | |
dc.date.available | NO_RESTRICTION | fr |
dc.date.available | 2022-10-31T13:33:52Z | |
dc.date.issued | 2021-05-25 | |
dc.identifier.uri | http://hdl.handle.net/1866/26997 | |
dc.rights | Ce document est mis à disposition selon les termes de la Licence Creative Commons
Paternité 4.0 International. / This work is licensed under a Creative Commons Attribution 4.0
International License. | |
dc.rights.uri | https://creativecommons.org/licenses/by/4.0/ | |
dc.subject | HDX-MS | fr |
dc.subject | Nucleotide binding | fr |
dc.subject | Phospho-regulation | fr |
dc.subject | Potassium-chloride co-transport | fr |
dc.subject | Solute carrier | fr |
dc.title | Phospho-regulation, nucleotide binding and ion access control in potassium-chloride cotransporters | fr |
dc.type | Article | fr |
dc.contributor.affiliation | Université de Montréal. Faculté de médecine. École de kinésiologie et des sciences de l'activité physique | fr |
dc.identifier.doi | 10.15252/embj.2020107294 | |
dcterms.abstract | Potassium-coupled chloride transporters (KCCs) play crucial roles
in regulating cell volume and intracellular chloride concentration.
They are characteristically inhibited under isotonic conditions via
phospho-regulatory sites located within the cytoplasmic termini.
Decreased inhibitory phosphorylation in response to hypotonic cell
swelling stimulates transport activity, and dysfunction of this
regulatory process has been associated with various human
diseases. Here, we present cryo-EM structures of human KCC3b
and KCC1, revealing structural determinants for phosphoregulation in both N- and C-termini. We show that phosphomimetic KCC3b is arrested in an inward-facing state in which
intracellular ion access is blocked by extensive contacts with the
N-terminus. In another mutant with increased isotonic transport
activity, KCC1D19, this interdomain interaction is absent, likely
due to a unique phospho-regulatory site in the KCC1 N-terminus.
Furthermore, we map additional phosphorylation sites as well as a
previously unknown ATP/ADP-binding pocket in the large Cterminal domain and show enhanced thermal stabilization of
other CCCs by adenine nucleotides. These findings provide fundamentally new insights into the complex regulation of KCCs and
may unlock innovative strategies for drug development. | fr |
dcterms.isPartOf | urn:ISSN:0261-4189 | fr |
dcterms.isPartOf | urn:ISSN:1460-2075 | fr |
dcterms.language | eng | fr |
UdeM.ReferenceFournieParDeposant | https://doi.org/10.15252/embj.2020107294 | fr |
UdeM.VersionRioxx | Version publiée / Version of Record | fr |
oaire.citationTitle | EMBO journal | fr |
oaire.citationVolume | 40 | fr |