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TTYH family members form tetrameric complexes at the cell membrane
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SYSNO ASEP 0561085 Druh ASEP J - Článek v odborném periodiku Zařazení RIV J - Článek v odborném periodiku Poddruh J Článek ve WOS Název TTYH family members form tetrameric complexes at the cell membrane Tvůrce(i) Melvin, E. (IL)
Kalaninová, Zuzana (MBU-M) ORCID, RID
Shlush, E. (IL)
Man, Petr (MBU-M) RID, ORCID
Giladi, M. (IL)
Haitin, Y. (IL)Číslo článku 886 Zdroj.dok. Communications Biology. - : Nature Publishing Group
Roč. 5, č. 1 (2022)Poč.str. 11 s. Jazyk dok. eng - angličtina Země vyd. GB - Velká Británie Klíč. slova Size-exclusion chromatograph ; tweety family ; auxiliary subunits ; anion channel ; in-vitro ; protein ; expressio ; gene ; homolog Vědní obor RIV CE - Biochemie Obor OECD Biochemistry and molecular biology CEP ED1.1.00/02.0109 GA MŠMT - Ministerstvo školství, mládeže a tělovýchovy Výzkumná infrastruktura CIISB II - 90127 - Masarykova univerzita Způsob publikování Open access Institucionální podpora MBU-M - RVO:61388971 UT WOS 000847709600002 EID SCOPUS 85136996769 DOI 10.1038/s42003-022-03862-3 Anotace Single-molecule microscopy and in situ cross-linking show that the conserved Tweety homolog (TTYH) proteins have an innate tetrameric organization at the cell membrane.The conserved Tweety homolog (TTYH) family consists of three paralogs in vertebrates, displaying a ubiquitous expression pattern. Although considered as ion channels for almost two decades, recent structural and functional analyses refuted this role. Intriguingly, while all paralogs shared a dimeric stoichiometry following detergent solubilization, their structures revealed divergence in their relative subunit orientation. Here, we determined the stoichiometry of intact mouse TTYH (mTTYH) complexes in cells. Using cross-linking and single-molecule fluorescence microscopy, we demonstrate that mTTYH1 and mTTYH3 form tetramers at the plasma membrane, stabilized by interactions between their extracellular domains. Using blue-native PAGE, fluorescence-detection size-exclusion chromatography, and hydrogen/deuterium exchange mass spectrometry (HDX-MS), we reveal that detergent solubilization results in tetramers destabilization, leading to their dissolution into dimers. Moreover, HDX-MS demonstrates that the extracellular domains are stabilized in the context of the tetrameric mTTYH complex. Together, our results expose the innate tetrameric organization of TTYH complexes at the cell membrane. Future structural analyses of these assemblies in native membranes are required to illuminate their long-sought cellular function.
Pracoviště Mikrobiologický ústav Kontakt Eliška Spurná, eliska.spurna@biomed.cas.cz, Tel.: 241 062 231 Rok sběru 2023 Elektronická adresa https://www.nature.com/articles/s42003-022-03862-3
Počet záznamů: 1