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Electron cryo-microscopy structure of the mechanotransduction channel NOMPC

Nature AOP - 15 hours 23 min ago

Nature advance online publication 26 June 2017. doi:10.1038/nature22981

Authors: Peng Jin, David Bulkley, Yanmeng Guo, Wei Zhang, Zhenhao Guo, Walter Huynh, Shenping Wu, Shan Meltzer, Tong Cheng, Lily Yeh Jan, Yuh-Nung Jan & Yifan Cheng

Mechanosensory transduction for senses such as proprioception, touch, balance, acceleration, hearing and pain relies on mechanotransduction channels, which convert mechanical stimuli into electrical signals in specialized sensory cells. How force gates mechanotransduction channels is a central question in the field, for which there are two major models. One is the membrane-tension model: force applied to the membrane generates a change in membrane tension that is sufficient to gate the channel, as in the bacterial MscL channel and certain eukaryotic potassium channels. The other is the tether model: force is transmitted via a tether to gate the channel. The transient receptor potential (TRP) channel NOMPC is important for mechanosensation-related behaviours such as locomotion, touch and sound sensation across different species including Caenorhabditis elegans, Drosophila and zebrafish. NOMPC is the founding member of the TRPN subfamily, and is thought to be gated by tethering of its ankyrin repeat domain to microtubules of the cytoskeleton. Thus, a goal of studying NOMPC is to reveal the underlying mechanism of force-induced gating, which could serve as a paradigm of the tether model. NOMPC fulfils all the criteria that apply to mechanotransduction channels and has 29 ankyrin repeats, the largest number among TRP channels. A key question is how the long ankyrin repeat domain is organized as a tether that can trigger channel gating. Here we present a de novo atomic structure of Drosophila NOMPC determined by single-particle electron cryo-microscopy. Structural analysis suggests that the ankyrin repeat domain of NOMPC resembles a helical spring, suggesting its role of linking mechanical displacement of the cytoskeleton to the opening of the channel. The NOMPC architecture underscores the basis of translating mechanical force into an electrical signal within a cell.

1,2,4-Triazolo-[1,5-a]pyridine HIF Prolylhydroxylase Domain-1 (PHD-1) Inhibitors With a Novel Monodentate Binding Interaction

J Med Chem - Sat, 06/24/2017 - 07:32

Journal of Medicinal ChemistryDOI: 10.1021/acs.jmedchem.7b00352

Halogen Bonding in Nucleic Acid Complexes

J Med Chem - Fri, 06/23/2017 - 06:46

Journal of Medicinal ChemistryDOI: 10.1021/acs.jmedchem.7b00329

Extensive Assessment of Various Computational Methods for Aspartate’s pKa Shift

JCIM - Thu, 06/22/2017 - 20:48

Journal of Chemical Information and ModelingDOI: 10.1021/acs.jcim.7b00177

Fibroblast Activation Protein α Activated Tripeptide Bufadienolide Antitumor Prodrug with Reduced Cardiotoxicity

J Med Chem - Thu, 06/22/2017 - 12:13

Journal of Medicinal ChemistryDOI: 10.1021/acs.jmedchem.6b01755

Strong constraints on aerosol–cloud interactions from volcanic eruptions

Nature - Wed, 06/21/2017 - 23:00

Strong constraints on aerosol–cloud interactions from volcanic eruptions

Nature 546, 7659 (2017). doi:10.1038/nature22974

Authors: Florent F. Malavelle, Jim M. Haywood, Andy Jones, Andrew Gettelman, Lieven Clarisse, Sophie Bauduin, Richard P. Allan, Inger Helene H. Karset, Jón Egill Kristjánsson, Lazaros Oreopoulos, Nayeong Cho, Dongmin Lee, Nicolas Bellouin, Olivier Boucher, Daniel P. Grosvenor, Ken S. Carslaw, Sandip Dhomse, Graham W. Mann, Anja Schmidt, Hugh Coe, Margaret E. Hartley, Mohit Dalvi, Adrian A. Hill, Ben T. Johnson, Colin E. Johnson, Jeff R. Knight, Fiona M. O’Connor, Daniel G. Partridge, Philip Stier, Gunnar Myhre, Steven Platnick, Graeme L. Stephens, Hanii Takahashi & Thorvaldur Thordarson

Aerosols have a potentially large effect on climate, particularly through their interactions with clouds, but the magnitude of this effect is highly uncertain. Large volcanic eruptions produce sulfur dioxide, which in turn produces aerosols; these eruptions thus represent a natural experiment through which to quantify

Protect funding for US earthquake early-warning system

Nature - Wed, 06/21/2017 - 20:45

Protect funding for US earthquake early-warning system

Nature 546, 7659 (2017). doi:10.1038/nature.2017.22162

Donald Trump’s proposed cuts to ShakeAlert puts the west coast at risk.

SEVEN DAYS

Nature - Wed, 06/21/2017 - 20:45

SEVEN DAYS

Nature 546, 7659 (2017). http://www.nature.com/doifinder/10.1038/546456a

The week in science: 16–22 June 2017.

China’s genomics giant to make stock-market debut

Nature - Wed, 06/21/2017 - 20:45

China’s genomics giant to make stock-market debut

Nature 546, 7659 (2017). http://www.nature.com/doifinder/10.1038/546461

Author: David Cyranoski

Once the world's biggest DNA sequencer for research, BGI is now looking to medical applications to boost profits.

How sea-floor sensors could save the world from natural disasters

Nature - Wed, 06/21/2017 - 20:45

How sea-floor sensors could save the world from natural disasters

Nature 546, 7659 (2017). http://www.nature.com/doifinder/10.1038/546466a

Author: Alexandra Witze

Geophysicists are racing to monitor underwater faults in Earth’s crust so they can provide warning of the next big earthquake and tsunami.

α-Conotoxin [S9A]TxID Potently Discriminates between α3β4 and α6/α3β4 Nicotinic Acetylcholine Receptors

J Med Chem - Wed, 06/21/2017 - 09:06

Journal of Medicinal ChemistryDOI: 10.1021/acs.jmedchem.7b00546

Track batteries degrading in real time

Nature - Tue, 06/20/2017 - 23:00

Track batteries degrading in real time

Nature 546, 7659 (2017). doi:10.1038/546469a

Authors: Liqiang Mai, Mengyu Yan & Yunlong Zhao

Monitor deforming electrodes to speed development of renewable-energy storage, write Liqiang Mai, Mengyu Yan and Yunlong Zhao.

Botany: He made plants a profession

Nature - Tue, 06/20/2017 - 23:00

Botany: He made plants a profession

Nature 546, 7659 (2017). doi:10.1038/546472a

Author: Jim Endersby

Jim Endersby revisits the legacy of trailblazing botanist Joseph Dalton Hooker.

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