{"file":[{"creator":"dernst","file_name":"2022_NatureCommunications_Herguedas.pdf","file_id":"10778","date_updated":"2022-02-21T07:59:32Z","success":1,"content_type":"application/pdf","date_created":"2022-02-21T07:59:32Z","checksum":"d86ee8eabe8b794730729ffbb1a8832e","access_level":"open_access","file_size":2625540,"relation":"main_file"}],"pmid":1,"article_processing_charge":"No","user_id":"4359f0d1-fa6c-11eb-b949-802e58b17ae8","isi":1,"department":[{"_id":"PeJo"}],"day":"08","publisher":"Springer Nature","date_created":"2022-02-20T23:01:30Z","abstract":[{"text":"AMPA-type glutamate receptors (AMPARs) mediate rapid signal transmission at excitatory\r\nsynapses in the brain. Glutamate binding to the receptor’s ligand-binding domains (LBDs)\r\nleads to ion channel activation and desensitization. Gating kinetics shape synaptic transmission\r\nand are strongly modulated by transmembrane AMPAR regulatory proteins (TARPs)\r\nthrough currently incompletely resolved mechanisms. Here, electron cryo-microscopy\r\nstructures of the GluA1/2 TARP-γ8 complex, in both open and desensitized states\r\n(at 3.5 Å), reveal state-selective engagement of the LBDs by the large TARP-γ8 loop (‘β1’),\r\nelucidating how this TARP stabilizes specific gating states. We further show how TARPs alter\r\nchannel rectification, by interacting with the pore helix of the selectivity filter. Lastly, we\r\nreveal that the Q/R-editing site couples the channel constriction at the filter entrance to the\r\ngate, and forms the major cation binding site in the conduction path. Our results provide a\r\nmechanistic framework of how TARPs modulate AMPAR gating and conductance.","lang":"eng"}],"volume":13,"file_date_updated":"2022-02-21T07:59:32Z","scopus_import":"1","_id":"10763","oa":1,"publication":"Nature Communications","language":[{"iso":"eng"}],"publication_status":"published","quality_controlled":"1","title":"Mechanisms underlying TARP modulation of the GluA1/2-γ8 AMPA receptor","date_published":"2022-02-08T00:00:00Z","citation":{"short":"B. Herguedas, B.K. Kohegyi, J.N. Dohrke, J. Watson, D. Zhang, H. Ho, S.A. Shaikh, R. Lape, J.M. Krieger, I.H. Greger, Nature Communications 13 (2022).","mla":"Herguedas, Beatriz, et al. “Mechanisms Underlying TARP Modulation of the GluA1/2-Γ8 AMPA Receptor.” <i>Nature Communications</i>, vol. 13, 734, Springer Nature, 2022, doi:<a href=\"https://doi.org/10.1038/s41467-022-28404-7\">10.1038/s41467-022-28404-7</a>.","ieee":"B. Herguedas <i>et al.</i>, “Mechanisms underlying TARP modulation of the GluA1/2-γ8 AMPA receptor,” <i>Nature Communications</i>, vol. 13. Springer Nature, 2022.","ama":"Herguedas B, Kohegyi BK, Dohrke JN, et al. Mechanisms underlying TARP modulation of the GluA1/2-γ8 AMPA receptor. <i>Nature Communications</i>. 2022;13. doi:<a href=\"https://doi.org/10.1038/s41467-022-28404-7\">10.1038/s41467-022-28404-7</a>","chicago":"Herguedas, Beatriz, Bianka K. Kohegyi, Jan Niklas Dohrke, Jake Watson, Danyang Zhang, Hinze Ho, Saher A. Shaikh, Remigijus Lape, James M. Krieger, and Ingo H. Greger. “Mechanisms Underlying TARP Modulation of the GluA1/2-Γ8 AMPA Receptor.” <i>Nature Communications</i>. Springer Nature, 2022. <a href=\"https://doi.org/10.1038/s41467-022-28404-7\">https://doi.org/10.1038/s41467-022-28404-7</a>.","apa":"Herguedas, B., Kohegyi, B. K., Dohrke, J. N., Watson, J., Zhang, D., Ho, H., … Greger, I. H. (2022). Mechanisms underlying TARP modulation of the GluA1/2-γ8 AMPA receptor. <i>Nature Communications</i>. Springer Nature. <a href=\"https://doi.org/10.1038/s41467-022-28404-7\">https://doi.org/10.1038/s41467-022-28404-7</a>","ista":"Herguedas B, Kohegyi BK, Dohrke JN, Watson J, Zhang D, Ho H, Shaikh SA, Lape R, Krieger JM, Greger IH. 2022. Mechanisms underlying TARP modulation of the GluA1/2-γ8 AMPA receptor. Nature Communications. 13, 734."},"tmp":{"name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","image":"/images/cc_by.png","short":"CC BY (4.0)","legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode"},"intvolume":"        13","year":"2022","month":"02","publication_identifier":{"eissn":["20411723"]},"author":[{"full_name":"Herguedas, Beatriz","first_name":"Beatriz","last_name":"Herguedas"},{"full_name":"Kohegyi, Bianka K.","last_name":"Kohegyi","first_name":"Bianka K."},{"full_name":"Dohrke, Jan Niklas","last_name":"Dohrke","first_name":"Jan Niklas"},{"first_name":"Jake","orcid":"0000-0002-8698-3823","last_name":"Watson","full_name":"Watson, Jake","id":"63836096-4690-11EA-BD4E-32803DDC885E"},{"full_name":"Zhang, Danyang","first_name":"Danyang","last_name":"Zhang"},{"full_name":"Ho, Hinze","first_name":"Hinze","last_name":"Ho"},{"first_name":"Saher A.","last_name":"Shaikh","full_name":"Shaikh, Saher A."},{"full_name":"Lape, Remigijus","first_name":"Remigijus","last_name":"Lape"},{"full_name":"Krieger, James M.","first_name":"James M.","last_name":"Krieger"},{"full_name":"Greger, Ingo H.","first_name":"Ingo H.","last_name":"Greger"}],"external_id":{"pmid":["35136046"],"isi":["000757297200008"]},"status":"public","date_updated":"2023-08-02T14:25:33Z","oa_version":"Published Version","doi":"10.1038/s41467-022-28404-7","has_accepted_license":"1","article_type":"original","type":"journal_article","acknowledgement":"We thank Ondrej Cais for critical reading of the manuscript. We are grateful to LMB\r\nscientific computing and the EM facility for support, Paul Emsley for help with model\r\nbuilding and Takanori Nakane for helpful comments with Relion 3.1. This work was\r\nsupported by grants from the Medical Research Council (MC_U105174197) and BBSRC\r\n(BB/N002113/1) to I.H.G, and grants from the MCIN/AEI/ 10.13039/501100011033 and\r\n“ESF Investing in your future” to B.H (PID2019-106284GA-I00 and RYC2018-025720-I).","article_number":"734","ddc":["570"]}