Membrane proteins articles within Nature Communications

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  • 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

    Studies on mechanotransduction are limited by our ability to apply low range forces to specific mechanoreceptors on cell membranes. Here the authors report the Nano-winch, a programmable DNA origami-based molecular actuator, to manipulate multiple mechanoreceptors in parallel by exerting piconewton forces.

    • A. Mills
    • , N. Aissaoui
    •  & G. Bellot

  • 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

    The myeloma cell surface proteome regulates plasma cell biology and delineates therapy targets. Here, the authors profile the myeloma surfaceome at baseline and in drug resistance, finding the potential target CCR10, and include a streamlined approach to primary sample analysis.

    • Ian D. Ferguson
    • , Bonell Patiño-Escobar
    •  & Arun P. Wiita

  • 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

    EGFR regulates cellular processes across the animal kingdom. Here, the authors show that transmembrane conformational coupling is the first step in EGFR signaling, providing evidence for the existence of transmembrane intramolecular conformational changes in a single pass membrane protein.

    • Shwetha Srinivasan
    • , Raju Regmi
    •  & Gabriela S. Schlau-Cohen

  • Article
    | Open Access

    Autophagy can selectively target cargo for degradation. Here the authors map the proximal interactome of ATG8-paralogs LC3B and LC3C uncovering an LC3C-Endocytic-Associated-Pathway that selectively recruits internalized plasma membrane cargo, Met and transferrin receptors, to nascent autophagosomes.

    • Paula P. Coelho
    • , Geoffrey G. Hesketh
    •  & Morag Park

  • Article
    | Open Access

    Excitatory amino acid transporter 2 (EAAT2) mediates glutamate uptake in the synapse. Here, authors report cryo-EM structures of the human EAAT2 in complexes with glutamate or selective inhibitor WAY-213613, revealing important insights into substrate recognition and selective inhibition.

    • Zhenglai Zhang
    • , Huiwen Chen
    •  & Yan Zhao

  • Article
    | Open Access

    Structural basis of V-ATPase regulation by endogenous proteins is unclear. Here, the authors find mEAK7 as an endogenous V-ATPase modulator and determine its structure with V-ATPase, suggesting the potential role of mEAK7 in V-ATPase regulation.

    • Rong Wang
    • , Yu Qin
    •  & Xiaochun Li

  • 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

    Human glucose transporters (GLUTs), particularly GLUT1 and GLUT3, are potential anticancer therapy targets. Here, Nan Wang et al. use an engineered GLUT 3 variant to identify an exofacial GLUT3 inhibitor, SA47, and elucidate the drug’s inhibitory mechanism.

    • Nan Wang
    • , Shuo Zhang
    •  & Nieng Yan

  • 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

    Although lipids are known to affect Hedgehog (Hh) signalling, the underlying mechanisms remain unclear. Here, the authors show that Canopy4 regulates membrane sterol lipid levels, with knockout mouse embryos exhibiting digit number changes and other Hh signalling-related developmental defects.

    • Megan Lo
    • , Amnon Sharir
    •  & Ophir D. Klein

  • Article
    | Open Access

    Bacterial cell wall enzymes and their precursors are critical targets for antibiotic development. Here, the authors investigate several biosynthetic enzymes with their substrates and show that the passage of substrates and products in the pathway is controlled by their relative binding affinities.

    • Abraham O. Oluwole
    • , Robin A. Corey
    •  & Carol V. Robinson

  • Article
    | Open Access

    Bacterial photosynthesis reflects the early stages of the evolution of photosynthesis. Here, the authors present a systematic study of the cryo-EM structures of the dimeric light harvesting–reaction center complexes and assembly variants from Rhodobacter sphaeroides, which delineated a hierarchical assembly pathway and quinone transport routes of the dimeric photosynthetic RC–LH1 core complex.

    • Peng Cao
    • , Laura Bracun
    •  & Lu-Ning Liu

  • Article
    | Open Access

    The structural basis for urokinase-type plasminogen activator receptor (uPAR) dimerization is not understood. Here, the authors solve the crystal structure of soluble uPAR dimers, identifying substantial structural changes compared to the monomer.

    • Shujuan Yu
    • , Yaqun Sui
    •  & Mingdong Huang

  • 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

  • Article
    | Open Access

    The nonopioid sigma-1 receptor (σ1R) is localized to the endoplasmic reticulum (ER), interacts with multiple effector proteins and various synthetic ligands, and is implicated in many diseases. Here, authors provide structural and functional evidence to reveal the likely ligand entry pathway for σ1R.

    • Fuhui Meng
    • , Yang Xiao
    •  & Xiaoming Zhou

  • Article
    | Open Access

    The rotary ATPases use a rotary catalytic mechanism to drive transmembrane proton movement powered by ATP hydrolysis. Here, the authors report a collection of V/A-ATPase V1 domain structures, providing insights into rotary mechanism of the enzyme and potentially other rotary motor proteins driven by ATP hydrolysis.

    • J. Kishikawa
    • , A. Nakanishi
    •  & K. Yokoyama

  • Article
    | Open Access

    ATPases are the macromolecular machines for cellular energy production. Here the authors investigate factors that govern the assembly of the F1 complex from a bacterial F-type ATPase and relate differences in activity of complexes assembled in cells and in vitro to structural changes.

    • Khanh Vu Huu
    • , Rene Zangl
    •  & Nina Morgner

  • Article
    | Open Access

    Adenylyl cyclases (ACs) generate the second messenger cAMP and play an important role in cellular signaling. Here, the authors use cryo-EM to trace the conformational changes resulting from binding to partial and full activators to one of these enzymes, AC9.

    • Chao Qi
    • , Pia Lavriha
    •  & Volodymyr M. Korkhov

  • Article
    | Open Access

    LtaA catalyzes glycolipid translocation by a ‘trap-and-flip’ mechanism, pointing to a shared mechanistic model among MFS lipid transporters. Asymmetric lateral openings allow access of the entire lipid substrate to the amphipathic central cavity.

    • Elisabeth Lambert
    • , Ahmad Reza Mehdipour
    •  & Camilo Perez

  • Article
    | Open Access

    The intracellular domain (ICD) of Cys-loop receptors mediates many of their functions, but no complete structure of a Cys-loop receptor ICD is available to date. Here, the authors combine NMR and ESR spectroscopy to determine the full-length ICD structures of the human α7 nicotinic acetylcholine receptor (α7nAChR).

    • Vasyl Bondarenko
    • , Marta M. Wells
    •  & Pei Tang

  • Article
    | Open Access

    Prestin, expressed in outer hair cell (OHC), belongs to the Slc26 transporter family and functions as a voltage-driven motor that drives OHC electromotility. Here, the authors report cryo-EM structure and characterization of gerbil prestin, with insights into its mechanism of action.

    • Carmen Butan
    • , Qiang Song
    •  & Joseph Santos-Sacchi

  • Article
    | Open Access

    The authors show that the mechanism of BAK activation in mitochondrial apoptosis involves cooperation between direct activation by BH3-only protein BID and BAK autoactivation, providing a unifying basis for BAK triggering by BH3 ligands.

    • Geetika Singh
    • , Cristina D. Guibao
    •  & Tudor Moldoveanu

  • Article
    | Open Access

    During pyroptosis, gasdermin D (GSDMD) forms plasma membrane pores that initiate cell lysis. Here, the authors develop optogenetically activatable human GSDMD to assess GSDMD pore behavior and show that they are dynamic and can close, which can be a pyroptosis regulatory mechanism.

    • Ana Beatriz Santa Cruz Garcia
    • , Kevin P. Schnur
    •  & Gary C. H. Mo

  • Article
    | Open Access

    The intrinsic flexibility of membranes proteins still poses a challenge in determining their active structure. Here the authors describe the development of a method that combines chemical footprinting and mass spectrometry to assist in determining the structure of native membrane proteins and their dynamics.

    • Jie Sun
    • , Xiaoran Roger Liu
    •  & Michael L. Gross

  • Article
    | Open Access

    Hedgehog-Interacting Protein (HHIP) is the only reported secreted inhibitor of Sonic Hedgehog (SHH) signalling. Here, the authors report structures of the HHIP N- and C-terminal domains, both in complexes with glycosaminoglycans, providing insights into the molecular basis for SHH sequestration and inhibition.

    • Samuel C. Griffiths
    • , Rebekka A. Schwab
    •  & Christian Siebold

  • Article
    | Open Access

    The β-barrel assembly machinery (BAM) assists the folding and membrane insertion of bacterial outer membrane proteins. Here, the authors report structural characterization of BAM in lipid environment and in complex with the client protein EspP integrated into the barrel of BamA, providing insight into BAM mechanism of function.

    • Runrun Wu
    • , Jeremy W. Bakelar
    •  & Nicholas Noinaj

  • Article
    | Open Access

    Eph receptor tyrosine kinases and their ephrin ligands mediate cell-cell communication. Here, the authors assess the structure and dynamics of the EphA2 intracellular region and uncover complex effects of phosphorylation within the linker region between EphA2 kinase and SAM domains.

    • Bernhard C. Lechtenberg
    • , Marina P. Gehring
    •  & Elena B. Pasquale

  • Article
    | Open Access

    Dispatched (Disp) RND transporter, activated by Furin-mediated proteolytic cleavage, mediates the release of the lipid-modified Hedgehog (Hh) ligands. Here, the authors report structures of human Disp1 (hDisp1) before and after cleavage, and in complex with lipid-modified Sonic hedgehog (Shh), with insights into the mechanisms of hDisp1 activation and function.

    • Wanqiu Li
    • , Linlin Wang
    •  & Xin Gong

  • Article
    | Open Access

    DNA transfer between two bacterial cells is mediated by the conjugative type 4 secretion systems (T4SSs). Here, the authors report the structure of a complete T4SS outer-membrane core complex (OMCC), revealing distinct C17 and C13 symmetries of its central inner and peripheral outer ring regions, respectively.

    • Himani Amin
    • , Aravindan Ilangovan
    •  & Tiago R. D. Costa

  • Article
    | Open Access

    Amphiphysin BAR proteins reshape membranes, but the dynamics of the process remained unexplored. Here, the authors show through experiment and modelling that reshaping depends on the initial template shape, occurs even at low initial curvature, and involves the coexistence of isotropic and nematic states.

    • Anabel-Lise Le Roux
    • , Caterina Tozzi
    •  & Pere Roca-Cusachs

  • Article
    | Open Access

    Terminal bd oxidases endow bacterial pathogens with resistance to cellular stressors. The authors report the structure of E. coli bd-II type oxidase with the bound inhibitor aurachin D, providing a structural basis for the design of specifically binding antibiotics.

    • Antonia Grauel
    • , Jan Kägi
    •  & Thorsten Friedrich

  • Article
    | Open Access

    New virions of Ff bacteriophages are extruded from the host cell via the channel built from phage protein pIV, homologous to bacterial secretins. Here, the authors report the structure of this channel from the f1 filamentous bacteriophage and propose its use as an adjuvant to increase the uptake and efficacy of antibiotics.

    • Rebecca Conners
    • , Mathew McLaren
    •  & Vicki A. M. Gold

  • Article
    | Open Access

    ABCA4 is an ATP-binding cassette (ABC) transporter that flips N-retinylidenephosphatidylethanolamine (N-Ret-PE) to the cytoplasmic leaflet of photoreceptor membranes. ABCA4 mutations are associated with loss of vision. Here, structures of ABCA4 with and without substrate bound provide insight into N-Ret-PE binding and suggest a lateral access mechanism.

    • Jessica Fernandes Scortecci
    • , Laurie L. Molday
    •  & Robert S. Molday

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