Permeation and transport articles within Nature Communications

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  • Article
    | Open Access

    TPC2 is an important organellar Na+/Ca2+ release channel which regulates function of lysosomes and lysosome-related organelles. Here, Wang et al. demonstrate that a gain-of-function mutation (R210C) in TPC2 leads to hypopigmentaion, enlarged endolysosomes, enhanced lysosomal Ca2+ release and hyper-acidification.

    • Qiaochu Wang
    • , Zengge Wang
    •  & Wei Li

  • Article
    | Open Access

    The potassium channel selectivity filter is responsible for conduction and selectivity of K + over other cations. Here, the authors use a combination of single molecule FRET, non-canonical fluorescent amino acid incorporation, and single channel patch-clamp electrophysiology, to establish the generality of K + -induced SF conformational stability across the K + channel superfamily.

    • Marcos Matamoros
    • , Xue Wen Ng
    •  & Colin G. Nichols

  • Article
    | Open Access

    pH sensation is critical for survival of vertebrates. Here, authors found six vertebrate OTOP1 channels that were highly conserved and directly activated by extracellular alkali. Key mutations of OTOP1 reduced alkali affinity without affecting acid activation.

    • Lifeng Tian
    • , Hao Zhang
    •  & Ren Lai

  • Article
    | Open Access

    To date, no Ca2 + -selective channelrhodopsins have been characterized. In this study, Fernandez Lahore et al. report two calcium-permeable channelrhodopsins (CapChR1 and 2) for the photocontrol of calcium signalling in excitable tissue.

    • Rodrigo G. Fernandez Lahore
    • , Niccolò P. Pampaloni
    •  & Peter Hegemann

  • Article
    | Open Access

    The authors present a wood formation model to explain multiple, hitherto poorly understood observations, related to carbon density, cell size, and temperature-growth relationships key for future carbon cycle simulations and past proxy interpretation.

    • Andrew D. Friend
    • , Annemarie H. Eckes-Shephard
    •  & Quinten Tupker

  • Article
    | Open Access

    It is currently debated how to reliably distinguish liquid–liquid phase separation (LLPS) from other mechanisms. Here the authors report model-free calibrated half-FRAP (MOCHA-FRAP) to probe the barrier at the condensate interface that is responsible for preferential internal mixing in LLPS.

    • Fernando Muzzopappa
    • , Johan Hummert
    •  & Fabian Erdel

  • Article
    | Open Access

    Antibiotic resistance through multidrug efflux is a major hurdle in antibiotic development. Here, authors experimentally demonstrate that EmrE, a small multidrug resistance efflux pump from E. coli, can confer resistance or susceptibility depending on the small molecule substrate.

    • Peyton J. Spreacker
    • , Nathan E. Thomas
    •  & Katherine A. Henzler-Wildman

  • Comment
    | Open Access

    In this work, Morgenstern and colleagues describe an approach involving functionalized nanobodies which decrease the activity of voltage-gated Ca2+ channels associated with β1 subunits and promote their removal from the surface membrane of neurons and muscle.

    • Declan Manning
    •  & L. Fernando Santana

  • Article
    | Open Access

    Auxiliary subunit molecular diversity is an unexploited target for developing ion channel inhibitors. Here, the authors develop a general approach to inhibit ion channels based on the resident auxiliary subunit isoform to elucidate unique functions of distinct ion channel macromolecular complexes.

    • Travis J. Morgenstern
    • , Neha Nirwan
    •  & Henry M. Colecraft

  • Article
    | Open Access

    CLC-type channels selectively transport Cl− across biological membranes, but it is unclear how discrimination between anions is maintained. Here, authors use a combination of non-natural amino acid substitutions, electrophysiology, and molecular dynamics simulations to determine Cl− specificity within this family of ion channels.

    • Lilia Leisle
    • , Kin Lam
    •  & Alessio Accardi

  • Article
    | Open Access

    TRPV2 is activated by temperature and cannabinoids. Here, the authors have used cryo-EM and electrophysiology to identify a cannabinoid binding site distinct from that of cannabidiol as a possible drug target for treatment of inflammation and immune-mediated diseases.

    • Liying Zhang
    • , Charlotte Simonsen
    •  & Peter M. Zygmunt

  • Article
    | Open Access

    Channelrhodopsin photoreceptors are responsible for phototaxis in C. reinhardtii. Here, authors introduce point mutations in the channel which modify photocycle kinetics and ion selectivity, resulting in a deeper understanding of phototaxis in low light conditions.

    • Olga Baidukova
    • , Johannes Oppermann
    •  & Peter Hegemann

  • Article
    | Open Access

    TMEM16F is a dual ion channel and lipid scramblase that is involved in blood coagulation and cell fusion. Here, authors elucidate how the protein is activated by Ca2+ to accomplish both functions in a single protein conformation.

    • Melanie Arndt
    • , Carolina Alvadia
    •  & Raimund Dutzler

  • Article
    | Open Access

    SGLT1 is essential for glucose, galactose and water uptake from the intestine, and its inhibitors have broad therapeutic potential. Here, the authors describe the cryo-EM structure of human SGLT1 in complex with an inhibitor.

    • Yange Niu
    • , Wenhao Cui
    •  & Lei Chen

  • Article
    | Open Access

    Rnf reversibly reduces NAD+ by ferredoxin coupled with Na+/H+ pumping for microbial ion gradient or reduced ferredoxin formation. Here, a cryo-EM structure provides information about the participating iron and flavin cofactors, the electron transfer route and the putative Na+ passage.

    • Stella Vitt
    • , Simone Prinz
    •  & Wolfgang Buckel

  • Article
    | Open Access

    The nuclear pore complex (NPC) barrier is a selective phase assembled from disordered but cohesive FG domains. The authors provide a thermodynamic description of an FG phase that is ultimately simplified and yet closely recapitulates NPC transport selectivity.

    • Sheung Chun Ng
    •  & Dirk Görlich

  • Article
    | Open Access

    Dispersive transport through complex media, relevant for semiconductors, liquid crystals, and biological soft matter, is influenced by their microscopic, porous structure. The authors consider the statistics of pore-junction units, in contrast to individual pores, to link morphology and macroscopic transport characteristics.

    • Felix J. Meigel
    • , Thomas Darwent
    •  & Karen Alim

  • Article
    | Open Access

    In this work, the authors report an ATP-dependent phosphatidylserine floppase activity for the lysosomal ATP-binding cassette transporter TAPL. In addition, they report the cryo-EM structures of mouse TAPL complexed with (i) phospholipid, (ii) cholesteryl hemisuccinate (CHS) and 9-mer peptide, and (iii) ADP·BeF3. Together, their results suggest that TAPL uses different mechanisms to function as a peptide translocase and a phosphatidylserine floppase.

    • Jun Gyou Park
    • , Songwon Kim
    •  & Mi Sun Jin

  • Article
    | Open Access

    Arabidopsis thaliana potassium channel AKT1 is responsible for primary K + uptake from soil, which is functionally activated through phosphorylation and negatively regulated by an α-subunit AtKC1. Here, the authors report the structures of AKT1 at different states, revealing a 2- fold to 4-fold symmetry switch at cytoplasmic domain associated with AKT1 activity regulation.

    • Yaming Lu
    • , Miao Yu
    •  & Guanghui Yang

  • Article
    | Open Access

    The Spns lipid transporters use ion gradients to drive substrate transport, including bioactive sphingolipids. Here, Dastvan et al. investigated how binding of protons powers the conformational changes that enable broad transport by a bacterial Spns.

    • Reza Dastvan
    • , Ali Rasouli
    •  & Emad Tajkhorshid

  • Article
    | Open Access

    P1B-type ATPases export excess transition metals from cells. Here, the authors report a molecular structure of CopA, a coppertransporting P1B-ATPase from A. fulgidus, in an inward-facing E1 conformation.

    • Nina Salustros
    • , Christina Grønberg
    •  & Pontus Gourdon

  • Article
    | Open Access

    ATP-binding cassette transporter A1 (ABCA1) drives phospholipid (PL) from the plasma membrane into extracellular apolipoprotein A-I, for the production of high density lipoprotein (HDL). Here, the authors use simulations to assess the mechanism of ABCA1 function and show that ABCA1 extracts lipid from the outer face of the plasma membrane.

    • Jere P. Segrest
    • , Chongren Tang
    •  & Jay W. Heinecke

  • Article
    | Open Access

    Mitochondrial Atm1 proteins play important roles in the maturation of certain cytosolic proteins. Here, the authors exploit cryo-EM to capture several structures of an Atm1. The findings shed new light on the molecular function of Atm1 transporters.

    • Ping Li
    • , Amber L. Hendricks
    •  & Pontus Gourdon

  • Article
    | Open Access

    Sodium-Potassium Pump (Na+/K+-ATPase, NKA) generates an electrochemical gradient of sodium and potassium ions across the plasma membrane by hydrolyzing ATP. Here, the authors report structures of human NKA providing insight into the cytoplasmic Na+ entrance and the cytoplasmic gate closure coupled to ATP hydrolysis.

    • Yingying Guo
    • , Yuanyuan Zhang
    •  & Qiang Zhou

  • Article
    | Open Access

    The mechanism of cold-activated TRPM8 channel activation remains unclear. Here, authors have determined structures of mouse TRPM8 in apo or ligand-bound states, providing insights into the activation of TRPM8 structures in different states.

    • Cheng Zhao
    • , Yuan Xie
    •  & Jiangtao Guo

  • Article
    | Open Access

    Cryo-EM often yields multiple protein conformations within a single dataset. Using the thermal titration methods and cryo-EM, Do Hoon Kwon et al. elucidate the conformational trajectory of the TRPV1 with resiniferatoxin (RTx) bound.

    • Do Hoon Kwon
    • , Feng Zhang
    •  & Seok-Yong Lee

  • Article
    | Open Access

    TRPV3 mediates cutaneous sensations such as itch and pain. Here authors present the cryo-EM structure of TRPV3 bound with local anesthetic which binds the channel in membrane portals that connect the membrane environment to the channel pore.

    • Arthur Neuberger
    • , Kirill D. Nadezhdin
    •  & Alexander I. Sobolevsky

  • Article
    | Open Access

    TMEM16A, a calcium-activated chloride channel involved in multiple cellular processes, is implicated in various diseases, but its pharmacology remains poorly understood. Here, the authors combine cryo-EM and electrophysiology to elucidate the mechanism of TMEM16A inhibition by the pore blocker 1PBC.

    • Andy K. M. Lam
    • , Sonja Rutz
    •  & Raimund Dutzler

  • Article
    | Open Access

    SUR2-containing KATP channels are drug targets for certain vasodilators. Here, the authors determine high-resolution cryo-EM structures of SUR2 in complex with two vasodilators, P1075 and levcromakalim, uncovering the mechanisms of these drugs.

    • Dian Ding
    • , Jing-Xiang Wu
    •  & Lei Chen

  • Article
    | Open Access

    Lipid scrambling is required for many cellular processes but the lipid-protein interactions that occur during transport are unknown. Using cryoEM and biochemical assays the authors show that membrane thinning is critical for lipid flipping.

    • Maria E. Falzone
    • , Zhang Feng
    •  & Alessio Accardi

  • Article
    | Open Access

    The dopamine transporter, DAT, controls dopamine signaling by facilitating its reuptake using the Na+ gradient as driving force. Here, the authors uncover that an antiport of K+ ions also contributes to setting the rate of DAT-mediated dopamine clearance.

    • Solveig G. Schmidt
    • , Mette Galsgaard Malle
    •  & Claus J. Loland

  • Article
    | Open Access

    How mechanical forces drive fluid transport in the kidney remains unclear. Here, the authors use a microfluidic platform to show that kidney epithelial cells generate hydraulic pressure gradients across the epithelium, and that the fluid flux is from apical to basal for normal cells, and inverted in autosomal dominant polycystic kidney disease cells.

    • Mohammad Ikbal Choudhury
    • , Yizeng Li
    •  & Sean X. Sun

  • Article
    | Open Access

    The permeability barrier of nuclear pores is formed by disordered and yet self-interacting FG repeat domains, whose sequence heterogeneity is a challenge for mechanistic insights. Here the authors overcome this challenge and characterize the protein’s dynamics by applying NMR techniques to an FG phase system that has been simplified to its essentials.

    • Eszter E. Najbauer
    • , Sheung Chun Ng
    •  & Loren B. Andreas

  • Article
    | Open Access

    IP3 receptors are intracellular calcium channels involved in numerous signaling pathways. Here, the authors present the cryo-EM structures of type-3 IP3 receptors in multiple gating conformations, including the active state revealing the molecular mechanism of the receptor activation.

    • Emily A. Schmitz
    • , Hirohide Takahashi
    •  & Erkan Karakas

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