@article {56204, title = {A genetically encoded near-infrared fluorescent calcium ion indicator.}, journal = {Nature Methods}, volume = {16}, year = {2019}, month = {2019 Jan 21}, pages = {171-4}, abstract = {

We report an intensiometric, near-infrared fluorescent, genetically encoded calcium ion (Ca) indicator (GECI) with excitation and emission maxima at 678 and 704 nm, respectively. This GECI, designated NIR-GECO1, enables imaging of Ca transients in cultured mammalian cells and brain tissue with sensitivity comparable to that of currently available visible-wavelength GECIs. We demonstrate that NIR-GECO1 opens up new vistas for multicolor Ca imaging in combination with other optogenetic indicators and actuators.

}, issn = {1548-7105}, doi = {10.1038/s41592-018-0294-6}, author = {Qian, Yong and Piatkevich, Kiryl D and Mc Larney, Benedict and Abdelfattah, Ahmed S and Mehta, Sohum and Murdock, Mitchell H and Gottschalk, Sven and Molina, Rosana S and Zhang, Wei and Chen, Yingche and Wu, Jiahui and Drobizhev, Mikhail and Hughes, Thomas E and Zhang, Jin and Schreiter, Eric R and Shoham, Shy and Razansky, Daniel and Boyden, Edward S and Campbell, Robert E} } @article {49325, title = {Cryo-EM structure of the polycystin 2-l1 ion channel.}, journal = {eLife}, volume = {7}, year = {2018}, month = {2018 Jul 13}, abstract = {

We report the near atomic resolution (3.3 {\r A}) of the human polycystic kidney disease 2-like 1 (polycystin 2-l1) ion channel. Encoded by PKD2L1, polycystin 2-l1 is a calcium and monovalent cation-permeant ion channel in primary cilia and plasma membranes. The related primary cilium-specific polycystin-2 protein, encoded by PKD2, shares a high degree of sequence similarity, yet has distinct permeability characteristics. Here we show that these differences are reflected in the architecture of polycystin 2-l1.

}, issn = {2050-084X}, doi = {10.7554/eLife.36931}, author = {Hulse, Raymond E and Li, Zongli and Huang, Rick K and Zhang, Jin and Clapham, David E} } @article {49057, title = {Structure of full-length human TRPM4.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, year = {2018}, month = {2018 Feb 20}, pages = {2377-82}, abstract = {

Transient receptor potential melastatin subfamily member 4 (TRPM4) is a widely distributed, calcium-activated, monovalent-selective cation channel. Mutations in human TRPM4 (hTRPM4) result in progressive familial heart block. Here, we report the electron cryomicroscopy structure of hTRPM4 in a closed, Na-bound, apo state at pH 7.5 to an overall resolution of 3.7 {\r A}. Five partially hydrated sodium ions are proposed to occupy the center of the conduction pore and the entrance to the coiled-coil domain. We identify an upper gate in the selectivity filter and a lower gate at the entrance to the cytoplasmic coiled-coil domain. Intramolecular interactions exist between the TRP domain and the S4-S5 linker, N-terminal domain, and N and C termini. Finally, we identify aromatic interactions via π-π bonds and cation-π bonds, glycosylation at an N-linked extracellular site, a pore-loop disulfide bond, and 24 lipid binding sites. We compare and contrast this structure with other TRP channels and discuss potential mechanisms of regulation and gating of human full-length TRPM4.

}, issn = {1091-6490}, doi = {10.1073/pnas.1722038115}, author = {Duan, Jingjing and Li, Zongli and Li, Jian and Santa-Cruz, Ana and Sanchez-Martinez, Silvia and Zhang, Jin and Clapham, David E} } @article {49371, title = {Structure of the mammalian TRPM7, a magnesium channel required during embryonic development.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, year = {2018}, month = {2018 Aug 14}, pages = {E8201-10}, abstract = {

The transient receptor potential ion channel subfamily M, member 7 (TRPM7), is a ubiquitously expressed protein that is required for mouse embryonic development. TRPM7 contains both an ion channel and an α-kinase. The channel domain comprises a nonselective cation channel with notable permeability to Mg and Zn Here, we report the closed state structures of the mouse TRPM7 channel domain in three different ionic conditions to overall resolutions of 3.3, 3.7, and 4.1 {\r A}. The structures reveal key residues for an ion binding site in the selectivity filter, with proposed partially hydrated Mg ions occupying the center of the conduction pore. In high [Mg], a prominent external disulfide bond is found in the pore helix, which is essential for ion channel function. Our results provide a structural framework for understanding the TRPM1/3/6/7 subfamily and extend the knowledge base upon which to study the diversity and evolution of TRP channels.

}, issn = {1091-6490}, doi = {10.1073/pnas.1810719115}, author = {Duan, Jingjing and Li, Zongli and Li, Jian and Hulse, Raymond E and Santa-Cruz, Ana and Valinsky, William C and Abiria, Sunday A and Krapivinsky, Grigory and Zhang, Jin and Clapham, David E} } @article {49344, title = {Structure of the mouse TRPC4 ion channel.}, journal = {Nature Communications}, volume = {9}, year = {2018}, month = {2018 Aug 06}, pages = {3102}, abstract = {

Members of the transient receptor potential (TRP) ion channels conduct cations into cells. They mediate functions ranging from neuronally mediated hot and cold sensation to intracellular organellar and primary ciliary signaling. Here we report a cryo-electron microscopy (cryo-EM) structure of TRPC4 in its unliganded (apo) state to an overall resolution of 3.3 {\r A}. The structure reveals a unique architecture with a long pore loop stabilized by a disulfide bond. Beyond the shared tetrameric six-transmembrane fold, the TRPC4 structure deviates from other TRP channels with a unique cytosolic domain. This unique cytosolic N-terminal domain forms extensive aromatic contacts with the TRP and the C-terminal domains. The comparison of our structure with other known TRP structures provides molecular insights into TRPC4 ion selectivity and extends our knowledge of the diversity and evolution of the TRP channels.

}, issn = {2041-1723}, doi = {10.1038/s41467-018-05247-9}, author = {Duan, Jingjing and Li, Jian and Zeng, Bo and Chen, Gui-Lan and Peng, Xiaogang and Zhang, Yixing and Wang, Jianbin and Clapham, David E and Li, Zongli and Zhang, Jin} }