The SERCA residue Glu340 mediates interdomain communication that guides Ca2+transport
| Autor: | Jesper V. Møller, Maxwell M. G. Geurts, Poul Nissen, Marc le Maire, Johannes D. Clausen, Maike Bublitz, Jens Peter Andersen, Robin A. Corey, Guillaume Lenoir, Cédric Montigny, Bertrand Arnou, Christine Jaxel |
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| Přispěvatelé: | Department of Biochemistry [Oxford], University of Oxford [Oxford], Aarhus University [Aarhus], Institut de Biologie Intégrative de la Cellule (I2BC), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS), Laboratoire des Protéines et Systèmes Membranaires (LPSM), Département Biochimie, Biophysique et Biologie Structurale (B3S), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS)-Institut de Biologie Intégrative de la Cellule (I2BC), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS), University of Oxford, I2BC, Centre National de la Recherche Scientifique (CNRS) |
| Jazyk: | angličtina |
| Rok vydání: | 2020 |
| Předmět: |
SERCA
[SDV]Life Sciences [q-bio] ATPase Mutant tryptophan fluorescence 01 natural sciences 03 medical and health sciences ATP hydrolysis 0103 physical sciences P-type ATPase Tryptophan fluorescence [SDV.BBM.BC]Life Sciences [q-bio]/Biochemistry Molecular Biology/Biochemistry [q-bio.BM] 030304 developmental biology 0303 health sciences Multidisciplinary 010304 chemical physics biology [SDV.BBM.BS]Life Sciences [q-bio]/Biochemistry Molecular Biology/Structural Biology [q-bio.BM] Chemistry Ca2+ binding Molecular dynamics simulations Cabinding molecular dynamics simulations Transmembrane domain Cytosol Biophysics biology.protein cardiovascular system Phosphorylation |
| Zdroj: | Geurts, M M G, Clausen, J D, Arnou, B, Montigny, C, Lenoir, G, Corey, R A, Jaxel, C, Møller, J V, Nissen, P, Andersen, J P, Le Maire, M & Bublitz, M 2020, ' The SERCA residue Glu340 mediates interdomain communication that guides Ca 2+ transport ', Proceedings of the National Academy of Sciences of the United States of America, vol. 117, no. 49, pp. 31114-31122 . https://doi.org/10.1073/pnas.2014896117 Proceedings of the National Academy of Sciences of the United States of America Proceedings of the National Academy of Sciences of the United States of America, National Academy of Sciences, 2020, 117 (49), pp.31114-31122. ⟨10.1073/pnas.2014896117⟩ Proceedings of the National Academy of Sciences of the United States of America, 2020, 117 (49), pp.31114-31122. ⟨10.1073/pnas.2014896117⟩ Proceedings of the National Academy of Sciences of the United States of America, National Academy of Sciences, 2020, ⟨10.1073/pnas.2014896117⟩ Proceedings of the National Academy of Sciences of the United States of America, 2020, ⟨10.1073/pnas.2014896117⟩ 'Proceedings of the National Academy of Sciences of the USA ', vol: 117, pages: 31114-31122 (2020) |
| ISSN: | 0027-8424 1091-6490 |
| Popis: | International audience; The sarco(endo)plasmic reticulum Ca 2+ -ATPase (SERCA) is a P-type ATPase that transports Ca 2+ from the cytosol into the sarco(endo)plasmic reticulum (SR/ER) lumen, driven by ATP. This primary transport activity depends on tight coupling between movements of the transmembrane helices forming the two Ca 2+ -binding sites and the cytosolic headpiece mediating ATP hydrolysis. We have addressed the molecular basis for this intramolecular communication by analyzing the structure and functional properties of the SERCA mutant E340A. The mutated Glu340 residue is strictly conserved among the P-type ATPase family of membrane transporters and is located at a seemingly strategic position at the interface between the phosphorylation domain and the cytosolic ends of 5 of SERCA’s 10 transmembrane helices. The mutant displays a marked slowing of the Ca 2+ -binding kinetics, and its crystal structure in the presence of Ca 2+ and ATP analog reveals a rotated headpiece, altered connectivity between the cytosolic domains, and an altered hydrogen bonding pattern around residue 340. Supported by molecular dynamics simulations, we conclude that the E340A mutation causes a stabilization of the Ca 2+ sites in a more occluded state, hence displaying slowed dynamics. This finding underpins a crucial role of Glu340 in interdomain communication between the headpiece and the Ca 2+ -binding transmembrane region. |
| Databáze: | OpenAIRE |
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