Membrane proteins articles within Nature Communications

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  • 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

  • Article
    | Open Access

    Lipid droplet biogenesis is orchestrated by the conserved membrane protein Seipin via an unknown mechanism. Here, the authors use structural, biochemical and molecular dynamics simulation approaches to reveal the mechanism of lipid droplet formation by the yeast Seipin Sei1 and its partner Ldb16.

    • Yoel A. Klug
    • , Justin C. Deme
    •  & Pedro Carvalho

  • Article
    | Open Access

    The TOM and TIM23 complexes facilitate the transport of nuclear-encoded proteins into the mitochondrial matrix. Here, the authors use a stalled client protein to purify the translocation supercomplex and gain insight into the TOM-TIM23 interface and the mechanism of protein handover from the TOM to the TIM23 complex.

    • Ridhima Gomkale
    • , Andreas Linden
    •  & Peter Rehling

  • Article
    | Open Access

    The mechanisms involved in SLC4-mediated ion transport are still under debate. Here, the authors present a cryoEM structure of the Sodium-driven Chloride/Bicarbonate Exchanger NDCBE, which - together with computational modeling and mutagenesis - reveals molecular determinants of ion transport by SLC4.

    • Weiguang Wang
    • , Kirill Tsirulnikov
    •  & Ira Kurtz

  • Article
    | Open Access

    Cytosolic amino acid concentrations are carefully maintained, but how homeostasis occurs is unclear. Here, the authors show that amino acid transporters primarily determine intracellular amino acid levels and develop a model that predicts a perturbation response similar to experimental data.

    • Gregory Gauthier-Coles
    • , Jade Vennitti
    •  & Stefan Bröer

  • Article
    | Open Access

    CD47 is a transmembrane receptor involved in the regulation of various signalling pathways and a promising target for immuno-oncology therapeutics. Here, the authors present the crystal structure of full-length human CD47 and provide insights into the molecular mechanism of CD47-mediated signalling.

    • Gustavo Fenalti
    • , Nicolas Villanueva
    •  & Kandasamy Hariharan

  • Article
    | Open Access

    The human Tweety homologue (TTYH) family of transmembrane proteins have been suggested to act as chloride channels. Here the authors present cryo-EM structures of the 3 human TTYH paralogs that do not display the expected features of an anion channel, and instead appear to interact with lipid-like compounds residing in the membrane; suggesting an involvement in lipid-associated processes.

    • Anastasiia Sukalskaia
    • , Monique S. Straub
    •  & Raimund Dutzler

  • Article
    | Open Access

    Lipins need to bind cell membranes before they can function as phosphatidic acid phosphatases. Here, the authors elucidate the structural basis of lipin membrane-association and identify a lipin domain with a novel protein fold that is critical for membrane binding and full functionality of lipins.

    • Weijing Gu
    • , Shujuan Gao
    •  & Michael V. Airola

  • Article
    | Open Access

    Bacteria can secrete diffusible protein toxins that kill competing bacteria. Here, the authors use biochemical, biophysical and structural analyses to show how one of these toxins exploits TolC (a major antibiotic efflux channel) to transport itself across the outer membrane of target cells.

    • Nicholas G. Housden
    • , Melissa N. Webby
    •  & Colin Kleanthous

  • Article
    | Open Access

    Hedgehog signaling is essential for bone formation. Here, the authors show that the transmembrane protein SLITRK5 is a negative regulator of hedgehog signaling in osteoblasts, suggesting it may be a potential therapeutic target to enhance bone formation.

    • Jun Sun
    • , Dong Yeon Shin
    •  & Matthew B. Greenblatt

  • Article
    | Open Access

    Pannexin 1 (PANX1) is a membrane channel mediating release of signaling molecules to the extracellular space. PANX1 can be activated by GPCRs. Here, the authors elucidate a non-canonical channel activation pathway by α1-adrenergic receptor that involves HDAC6- mediated lysine deacetylation of PANX1.

    • Yu-Hsin Chiu
    • , Christopher B. Medina
    •  & Douglas A. Bayliss

  • Article
    | Open Access

    HAP2 is essential for gamete fusion during fertilization and is conserved among eukaryotes. Here the authors show that species-specific adhesion between Chlamydomonas plus and minus gametes initiates HAP2 to undergo a fusogenic conformational change into homotrimers via a molecular mechanism akin to that of enveloped viruses.

    • Jun Zhang
    • , Jennifer F. Pinello
    •  & William J. Snell

  • Article
    | Open Access

    The cryo-EM structure of pentameric green-light absorbing proteorhodopsin together with molecular dynamics simulations and functional studies provides insights into the proton translocation pathway and oligomerization, and a protonation-dependent mechanism for intracellular half channel hydration.

    • Stephan Hirschi
    • , David Kalbermatter
    •  & Dimitrios Fotiadis

  • Article
    | Open Access

    CNNM/CorB proteins are a conserved family of membrane proteins associated with Mg2+ transport. Here, structures of an archaeal CorB protein in apo state and with Mg2+-ATP bound and accompanying biophysical experiments suggest direct Mg2+ transport by CorB proteins.

    • Yu Seby Chen
    • , Guennadi Kozlov
    •  & Kalle Gehring

  • Article
    | Open Access

    Type-III secretion systems (T3SSs) are capable of translocating proteins with high speed while maintaining the membrane barrier for small molecules. Here, a structure-function analysis of the T3SS pore complex elucidates the precise mechanisms enabling the gating and the conformational changes required for protein substrate secretion.

    • Svenja Hüsing
    • , Manuel Halte
    •  & Thibaud T. Renault

  • Article
    | Open Access

    In human cells, P5B‐ATPases execute export of spermine from lysosomes to the cytosol, but the mechanisms of spermine recognition, uptake and transport remain elusive. Here the authors present cryo‐EM structures of a yeast homolog of human ATP13A2‐5, Ypk9, which depict three separate transport cycle intermediates, including spermine‐bound conformations

    • Ping Li
    • , Kaituo Wang
    •  & Pontus Gourdon

  • Article
    | Open Access

    Here, cryo-EM structures of human retinal ABCA4 transporter, either in apo state, in complex with ATP or with the physiological lipid substrate N-retinylidene-phosphatidylethanolamine (NRPE), reveal lateral opening, substrate recognition and suggest ‘lateral access and extrusion’ mechanism for ABCA-mediated lipid transport.

    • Tian Xie
    • , Zike Zhang
    •  & Xin Gong

  • Article
    | Open Access

    Sodium/proton exchanger 1 (NHE1) and its obligate binding partner Calcineurin B-homologous protein 1 (CHP1) regulate intracellular pH and volume homeostasis. Structures of the human NHE1-CHP1 complex offer insight into the regulation of NHE1 pH-sensitivity by CHP1 and into the interactions with NHE1 inhibitors.

    • Yanli Dong
    • , Yiwei Gao
    •  & Yan Zhao

  • Article
    | Open Access

    Secreted class 3 semaphorins (Sema3s) form tripartite complexes with a plexin receptor and neuropilin co-receptor to transduce signals for neuronal axon guidance and other processes. Here, the authors present the cryo-EM structure of the extracellular Sema3A/PlexinA4/Neuropilin1 complex that provides further insights into the interactions among semaphorin, plexin and neuropilin and reveals long flexible linkers in semaphorin and neuropilin that are important for complex formation.

    • Defen Lu
    • , Guijun Shang
    •  & Xuewu Zhang

  • Article
    | Open Access

    Microsomal glutathione S-transferase 2 (MGST2) produces leukotriene C4, an intracrine mediator of cell death. Structural, biochemical and computational analyses of human MGST2 suggest a mechanism employed by the enzyme to restrict catalysis to only one active site within the MGST2 trimer.

    • Madhuranayaki Thulasingam
    • , Laura Orellana
    •  & Jesper Z. Haeggström

  • Article
    | Open Access

    Bafilomycin A1, a member of macrolide antibiotics and an autophagy inhibitor, serves as a specific and potent V-ATPases inhibitor. Here authors report the cryo-EM structure of bafilomycin A1-bound V-ATPase with six bafilomycin A1 molecules bound to the c-ring and reveal the molecular basis for Bafilomycin A1 inhibition of the V-ATPase.

    • Rong Wang
    • , Jin Wang
    •  & Xiaochun Li

  • Article
    | Open Access

    Virulent type III secretion systems (T3SSs) or injectisomes enable pathogenic bacteria to inject effector proteins directly into the host cell cytoplasm. Structures of a needle complex engaged with the effector protein reveal the complete secretion channel and provide insights into the mechanism of substrate translocation through T3SSs.

    • Sean Miletic
    • , Dirk Fahrenkamp
    •  & Thomas C. Marlovits

  • Article
    | Open Access

    Glucocorticoid-induced tumor necrosis factor receptor-related protein (GITR) and GITR ligand (GITRL) regulate immune cell activities, including anti-tumor immune responses. Structures and visualization of human and mouse GITR–GITRL complexes offer insight into the architecture of higher-order membrane assemblies, and their signaling.

    • Feng Wang
    • , Bryant Chau
    •  & Pavel Strop

  • Article
    | Open Access

    Caveolae are spherical nanodomains of the plasma membrane generated by assembly of caveolin and cavin proteins. Here, the authors show that fuzzy electrostatic interactions between caveolin-1 and Cavin1 proteins, combined with membrane lipid interactions, are required to generate membrane curvature and a metastable caveola coat.

    • Vikas A. Tillu
    • , James Rae
    •  & Brett M. Collins

  • Article
    | Open Access

    Respiratory chains generate the proton motive force used for ATP synthesis. Cryo-EM structures of functional respiratory CIII2CIV supercomplex and native CIII2 from Rhodobacter capsulatus provide insight into CIII2CIV assembly and respiratory electron transport pathways in Gram-negative bacteria.

    • Stefan Steimle
    • , Trevor van Eeuwen
    •  & Fevzi Daldal

  • Article
    | Open Access

    The guided entry of tail-anchored proteins (GET) pathway assists in the delivery of such proteins to the ER. Here, the authors reveal that the pathway components Get4/5 probe a region near the ribosomal exit tunnel. Upon emergence of a client protein, Get4/5 recruits Sgt2 and initiates the targeting phase of the pathway.

    • Ying Zhang
    • , Evelina De Laurentiis
    •  & Sabine Rospert

  • Article
    | Open Access

    Archaerhodopsin-3 (AR3) mutants are commonly used in optogenetics for neuron silencing and membrane voltage sensing. High-resolution crystal structures show that desensitization of the AR3 photoreceptor occurs when internal hydrogen-bonded water networks are modified in response to changes in chromophore isomerization.

    • Juan F. Bada Juarez
    • , Peter J. Judge
    •  & Anthony Watts

  • Article
    | Open Access

    The endoplasmic reticulum network consists of tubules with high membrane curvature in cross-section, generated by the reticulons and REEPs, but how they introduce curvature is poorly understood. Here authors show that REEPs form homodimers and use their amphipathic helix and trans-membrane segments to introduce high membrane curvature that can even lead to the formation of lipoprotein particles.

    • Ning Wang
    • , Lindsay D. Clark
    •  & Tom A. Rapoport

  • Article
    | Open Access

    XylE is a bacterial xylose transporter and homologue of human glucose transporters GLUTs 1-4. HDX-MS, mutagenesis and MD simulations suggest that protonation of a conserved aspartate triggers conformational transition from outward- to inward facing state only in the presence of substrate xylose. In contrast, inhibitor glucose locks the transporter in the outward facing state.

    • Ruyu Jia
    • , Chloe Martens
    •  & Argyris Politis

  • Article
    | Open Access

    Gdx-Clo is a bacterial transporter from the small multidrug resistance (SMR) family. Here, the authors use solid supported membrane electrophysiology to characterize Gdx-Clo functionally and report crystal structures of Gdx-Clo which confirm the dual topology architecture and offer insight into substrate binding and transport mechanism.

    • Ali A. Kermani
    • , Christian B. Macdonald
    •  & Randy B. Stockbridge

  • Article
    | Open Access

    Cholesterol-dependent cytolysins (CDCs) are bacterial pore-forming virulence factors. Cryo-EM structure of an early conformation of the CDC ILY from Streptococcus intermedius, bound to the human immune receptor CD59, provides insight into ILY oligomerization and role of cholesterol in membrane lysis.

    • Nita R. Shah
    • , Tomas B. Voisin
    •  & Doryen Bubeck

  • Article
    | Open Access

    AcrB is a prototypical resistance–nodulation–division (RND) bacterial transporter, conferring resistance to a variety of antibiotics. HDX-MS and other, complementary approaches offer insight into AcrB structural dynamics and suggest the molecular mechanisms underlying drug export and inhibition of this multidrug-resistance conferring pump.

    • Eamonn Reading
    • , Zainab Ahdash
    •  & Argyris Politis

  • Article
    | Open Access

    The tripartite multidrug efflux system MexAB-OprM is a major actor in Pseudomonas aeruginosa antibiotic resistance by exporting a large variety of antimicrobial compounds. Here authors present cryo-EM structures of MexB at various stages of the assembly process and provide evidence that MexB activation is mediated by OprM and MexA.

    • Marie Glavier
    • , Dhenesh Puvanendran
    •  & Olivier Lambert

  • Article
    | Open Access

    Peroxiredoxin 2 (Prx2) was previously shown to transfer H2O2-derived oxidative equivalents to STAT3, generating disulfide-linked dimers and tetramers. Here the authors show that the interaction between Prx2 and STAT3 at the plasma membrane is mediated by the membrane chaperone annexin A2; suggesting that the redox relay complex is part of a membrane signaling domain.

    • Deepti Talwar
    • , Joris Messens
    •  & Tobias P. Dick

  • Article
    | Open Access

    The ATPase SecA drives Sec-dependent protein translocation across the bacterial plasma membrane. Here, the authors combine kinetic translocation measurements with single-molecule force spectroscopy and demonstrate that the SecA motor generates mechanical force to unfold and translocate preproteins.

    • Riti Gupta
    • , Dmitri Toptygin
    •  & Christian M. Kaiser

  • Article
    | Open Access

    Plexins are the receptors for the guidance molecules semaphorins and regulate immunity and the development of the nervous and cardiovascular systems. Here authors present a structure of full-length human PlexinC1 in complex with its ligand A39R, which reveals how inter-domain interactions couple extracellular ligand binding to receptor activation and signaling.

    • Yi-Chun Kuo
    • , Hua Chen
    •  & Xuewu Zhang

  • Article
    | Open Access

    Lipin/Pah phosphatidic acid phosphatases generate diacylglycerol to regulate triglyceride synthesis and cellular signaling. Here authors determine structures of Tetrahymena thermophila Pah2 and identify an N-terminal amphipathic helix essential for membrane association.

    • Valerie I. Khayyo
    • , Reece M. Hoffmann
    •  & Michael V. Airola

  • Article
    | Open Access

    Glutamate transporters are membrane transporters that clear the neurotransmitter L-glutamate from the synaptic cleft via a so-called elevator mechanism. Here the authors present five cryo-EM structures of the transporter homologue GltTk, which explain how substrate leakage is prevented.

    • Valentina Arkhipova
    • , Albert Guskov
    •  & Dirk J. Slotboom

  • Article
    | Open Access

    Formylpeptide receptors (FPRs) are a class of chemotactic G protein-coupled receptors (GPCRs) that recognize pathogen- and host-derived formylpeptides. Here the authors report the 3.17 Å cryo-EM structure of the human FPR2-Gi signaling complex with a bound peptide agonist and in combination with computational docking and MD simulations provide mechanistic insights into formylpeptide recognition by FPRs.

    • Youwen Zhuang
    • , Heng Liu
    •  & Cheng Zhang

  • Article
    | Open Access

    The β1-adrenergic receptor (β1AR) is a G-protein-coupled receptor (GPCRs) that binds catecholamine ligands. Here the authors employ site-specific labelling and 19F NMR measurements to characterise the structural changes and dynamics in the cytoplasmic region of β1AR upon agonist stimulation and coupling to a Gs-protein-mimetic nanobody.

    • J. Niclas Frei
    • , Richard W. Broadhurst
    •  & Daniel Nietlispach

  • Article
    | Open Access

    Detergents are indispensable reagents in membrane protein structural biology. Here, L. H. Urner and co-workers introduce oligoglycerol detergents (OGDs) and use native mass spectrometry to show how interactions of membrane proteins with native membrane lipids can be preserved during purification.

    • Leonhard H. Urner
    • , Idlir Liko
    •  & Kevin Pagel

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