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dc.contributor.authorOxenoid, Kirillen_US
dc.contributor.authorDong, Yingen_US
dc.contributor.authorCao, Chanen_US
dc.contributor.authorCui, Tanxingen_US
dc.contributor.authorSancak, Yaseminen_US
dc.contributor.authorMarkhard, Andrew L.en_US
dc.contributor.authorGrabarek, Zenonen_US
dc.contributor.authorKong, Liangliangen_US
dc.contributor.authorLiu, Zhijunen_US
dc.contributor.authorOuyang, Boen_US
dc.contributor.authorCong, Yaoen_US
dc.contributor.authorMootha, Vamsi K.en_US
dc.contributor.authorChou, James J.en_US
dc.date.accessioned2016-12-02T15:24:57Z
dc.date.issued2016en_US
dc.identifier.citationOxenoid, K., Y. Dong, C. Cao, T. Cui, Y. Sancak, A. L. Markhard, Z. Grabarek, et al. 2016. “Architecture of the Mitochondrial Calcium Uniporter.” Nature 533 (7602): 269-273. doi:10.1038/nature17656. http://dx.doi.org/10.1038/nature17656.en
dc.identifier.issn0028-0836en
dc.identifier.urihttp://nrs.harvard.edu/urn-3:HUL.InstRepos:29626111
dc.description.abstractMitochondria from multiple, eukaryotic clades uptake and buffer large amounts of calcium (Ca2+) via an inner membrane transporter called the uniporter. Early studies demonstrated that this transport requires a mitochondrial membrane potential and that the uniporter is itself Ca2+ activated, and blocked by ruthenium red or Ru3601. Later, electrophysiological studies demonstrated that the uniporter is an ion channel with remarkably high conductance and selectivity2. Ca2+ entry into mitochondria is also known to activate the TCA cycle and appears to be critical for matching ATP production in mitochondria with its cytosolic demand3. MCU (mitochondrial calcium uniporter) is the pore forming and Ca2+ conducting subunit of the uniporter, but its primary sequence does not resemble any calcium channel known to date. Here, we report the structure of the core region of MCU, determined using nuclear magnetic resonance (NMR) and electron microscopy (EM). MCU is a homo-oligomer with the second transmembrane helix forming a hydrophilic pore across the membrane. The channel assembly represents a new solution of ion channel architecture and is stabilized by a coiled coil motif protruding in the mitochondrial matrix. The critical DxxE motif forms the pore entrance featuring two carboxylate rings, which appear to be the selectivity filter based on the ring dimensions and functional mutagenesis. To our knowledge, this is one of the largest structures characterized by NMR, which provides a structural blueprint for understanding the function of this channel.en
dc.language.isoen_USen
dc.relation.isversionofdoi:10.1038/nature17656en
dc.relation.hasversionhttp://www.ncbi.nlm.nih.gov/pmc/articles/PMC4874835/pdf/en
dash.licenseLAAen_US
dc.titleArchitecture of the Mitochondrial Calcium Uniporteren
dc.typeJournal Articleen_US
dc.description.versionVersion of Recorden
dc.relation.journalNatureen
dash.depositing.authorCao, Chanen_US
dc.date.available2016-12-02T15:24:57Z
dc.identifier.doi10.1038/nature17656*
dash.authorsorderedfalse
dash.contributor.affiliatedChou, James
dash.contributor.affiliatedCao, Chan
dash.contributor.affiliatedSancak, Yasemin
dash.contributor.affiliatedMootha, Vamsi


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