Membrane proteins articles within Nature Communications

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  • Article
    | Open Access

    Human multidrug resistance protein 5 (hMRP5) effluxes anticancer and antivirus drugs, driving multidrug resistance. Here, the authors present cryo-EM structures of hMRP5 in different states, showing that hMRP5 can be autoinhibited by a short peptide from its N-terminal tail, which prevents the entry of substrates into hMRP5’s transport pathway.

    • Ying Huang
    • , Chenyang Xue
    •  & Zhongmin Liu

  • Article
    | Open Access

    Intracellular potassium (K+) homeostasis is achieved by activity of both ion channels and transporters. Here, the authors report structures of E. coli glutathione (GSH)-gated K+ efflux transporter KefC with bound K+ and conclude that the ion-binding site is adapted for binding a dehydrated ion.

    • Ashutosh Gulati
    • , Surabhi Kokane
    •  & David Drew

  • Article
    | Open Access

    Efflux pumps confer antibiotic resistance by coupling proton import with drug export. In this work, the authors uncover the proton-coupled transport mechanism for the clinically relevant efflux pump NorA from the pathogenic bacterium S. aureus.

    • Jianping Li
    • , Yan Li
    •  & Nathaniel J. Traaseth

  • Article
    | Open Access

    Sialin transports multiple substrates including sialic acid out of lysosomes, and neurotransmitters into synaptic vesicles. This study reports the cryo-EM structures of Sialin in multiple states revealing its transport and pH-sensing mechanisms.

    • Philip Schmiege
    • , Linda Donnelly
    •  & Xiaochun Li

  • Article
    | Open Access

    Here, authors classify genes flanking the Heliorhodopsin (HeR)-encoding genes and identify highly conserved residues for protein–protein interactions, revealing a function of HeR as regulatory rhodopsin for multidrug resistance.

    • Shin-Gyu Cho
    • , Ji-Hyun Kim
    •  & Kwang-Hwan Jung

  • Article
    | Open Access

    NADPH oxidase 5 (NOX5) is activated by Ca2+ signaling, catalyzing superoxide production by transferring electrons from intracellular NADPH to extracellular oxygen. Here the authors uncover the molecular basis of NOX5 activation and electron transfer.

    • Chenxi Cui
    • , Meiqin Jiang
    •  & Ji Sun

  • Article
    | Open Access

    The amino acid transporter complex LAT1-4F2hc is considered a major drug target for many cancers. Here, the authors apply native mass spectrometry-based approaches to decode a complete LAT1-4F2hc assembly. To do this, they connect post-translational modification and endogenous phospholipid binding to super-dimerization, function and localisation of LAT1-4F2hc.

    • Di Wu
    • , Renhong Yan
    •  & Carol V. Robinson

  • Article
    | Open Access

    SLC26A2 transports crucial ions and mutations in it cause diverse diseases. Here, authors present cryo-EM structures of SLC26A2 with substrates, revealing details of its homodimer assembly, dynamic substrate binding, and effects of mutations.

    • Wenxin Hu
    • , Alex Song
    •  & Hongjin Zheng

  • Article
    | Open Access

    The human Asc-1-4F2hc complex plays an important role in the neural development and stability. Here, authors determine the cryo-EM structures of Asc-1-4F2hc complex in three states, revealing its substrate recognition and transport mechanism.

    • Yaning Li
    • , Yingying Guo
    •  & Renhong Yan

  • Article
    | Open Access

    Asc1/CD98hc is a key regulator of small neutral amino acid transport in the brain and adipose tissue. Here, authors report the structure of semi-occluded hAsc1/CD98hc and provide a model for Asc1 exchange and facilitated diffusion modes of transport.

    • Josep Rullo-Tubau
    • , Maria Martinez-Molledo
    •  & Oscar Llorca

  • Article
    | Open Access

    The Epidermal Growth Factor Receptor (EGFR) is frequently found to be mutated in non-small cell lung cancer. Here, the authors show that EGFR lung cancer mutations promote the assembly of kinase-active dimers within ligand-free EGFR oligomers. These dimers bind ligand with high affinity and promote tumor growth.

    • R. Sumanth Iyer
    • , Sarah R. Needham
    •  & Marisa L. Martin-Fernandez

  • Article
    | Open Access

    ERGIC-53 engages in the ER-to-Golgi transport of secretory and membrane proteins by unknown mechanisms. Here authors report a long flexible tetrameric structure of full-length ERGIC-53 complexed with its functional partner MCFD2 by cryo-EM.

    • Satoshi Watanabe
    • , Yoshiaki Kise
    •  & Kenji Inaba

  • Article
    | Open Access

    The ABC transporter MRP2/ABCC2 is a polyspecific efflux transporter of organic anions expressed in hepatocyte canalicular membranes. Dysfunction leads to Dubin-Johnson syndrome. Here the authors provide structural and biochemical evidence on the modulation of MRP2 by intracellular kinases and inhibition by therapeutic drugs.

    • Tiziano Mazza
    • , Theodoros I. Roumeliotis
    •  & Konstantinos Beis

  • Article
    | Open Access

    The type VI secretion system (T6SS) of Gram-negative bacteria is typically anchored to the cell envelope through a membrane complex (MC), but Bacteroidota appear to lack genes encoding canonical MC components. Here, Bongiovanni et al. identify the Bacteroidota MC and study its biogenesis and connections with the conserved T6SS components.

    • Thibault R. Bongiovanni
    • , Casey J. Latario
    •  & Eric Durand

  • Article
    | Open Access

    Here the authors report structures of pendrin, an anion exchanger, in complex with its substrate Cl−, I−, or HCO3−, which reveal two anion binding sites in each protomer. The authors also identify binding sites of a pendrin inhibitor, niflumic acid.

    • Lie Wang
    • , Anthony Hoang
    •  & Ming Zhou

  • Article
    | Open Access

    Gram-negative bacteria rely on the Ton system for nutrient uptake. Here, authors uncover how the ExbD protein acts as a conformational switch and the function of peptidoglycan in order to energize this transport process across the outer membrane.

    • Maximilian Zinke
    • , Maylis Lejeune
    •  & Nadia Izadi-Pruneyre

  • Article
    | Open Access

    Rhodopsins are ubiquitous light-driven membrane proteins that have diverse functions in nature, and value as optogenetics tools. Here the authors characterise type 1 viral channelrhodopsins, showing that they regulate intracellular calcium and can be used for the photocontrol of muscle contraction in vivo.

    • Ana-Sofia Eria-Oliveira
    • , Mathilde Folacci
    •  & Michel Vivaudou

  • Article
    | Open Access

    Maintenance of lipid asymmetry in the bacterial outer membrane (OM) is mediated by the OmpC-Mla system, but mechanistic details remain to be elucidated. Here, the authors show that electrostatic interactions, conformational dynamics, and membrane thinning may facilitate spontaneous retrograde phospholipid transfer at the OM.

    • Jiang Yeow
    • , Min Luo
    •  & Shu-Sin Chng

  • Article
    | Open Access

    Using a freestanding planar lipid membrane system, the authors show that liquid-like protein condensates on one side of a lipid membrane colocalize with those on the opposite side, suggesting a mechanism of information transfer across biological membranes.

    • Yohan Lee
    • , Sujin Park
    •  & Jeanne C. Stachowiak

  • Article
    | Open Access

    Asymmetric phospholipid distribution in cell membranes is vital for cellular function. Here, authors reveal how ATP8B1, a P4-ATPase, can transport different lipids, including phosphatidylinositol.

    • Thibaud Dieudonné
    • , Felix Kümmerer
    •  & Poul Nissen

  • Article
    | Open Access

    Tail-anchored (TA) membrane protein biogenesis is mediated by the GET insertase. Here, authors present cryo-EM and X-ray structures, MD simulations and functional data for human and fungal insertases showing membrane remodeling for TA insertion.

    • Melanie A. McDowell
    • , Michael Heimes
    •  & Irmgard Sinning

  • Article
    | Open Access

    BSEP (ABCB11) is expressed in hepatocytes and extrudes bile salts into the canaliculi of the liver. Here, authors report cryo-EM structures of BSEP providing structural and functional insight into the mechanism of bile salt extrusion and small-molecule inhibition.

    • Hongtao Liu
    • , Rossitza N. Irobalieva
    •  & Kaspar P. Locher

  • Article
    | Open Access

    The structure of a bacterial membrane protein complex involved in the bioremediation of tetrachloroethene, a major chlorinated organic pollutant, was determined. It elucidates the path of electrons from menaquinol to the active site of the enzyme.

    • Lorenzo Cimmino
    • , Américo G. Duarte
    •  & Julien Maillard

  • Article
    | Open Access

    Inositol 1,4,5-trisphosphate receptors (IP3Rs) are intracellular Ca2+ channels that produce Ca2+ oscillations in response to GPCR and RTK activation. Here, Paknejad et al. resolve the conformational landscape of IP3Rs that gives rise to the biphasic dependence on Ca2+ for channel activity.

    • Navid Paknejad
    • , Vinay Sapuru
    •  & Richard K. Hite

  • Article
    | Open Access

    Insulin hormones and their receptors regulate key life processes in animals: from metabolism to life span. Human insulin receptor has been studied extensively. Here, the authors show remarkable structural similarity of fruit fly and human insulin receptors, indicating their universal functioning.

    • Cristina M. Viola
    • , Orsolya Frittmann
    •  & Andrzej M. Brzozowski

  • Article
    | Open Access

    Mycobacterial Mce systems are putative ABC transporters for lipids. Here, the authors revealed two distinct Mce1 complexes comprising different heterohexameric substrate binding assemblies that are negatively regulated via a novel mechanism.

    • Yushu Chen
    • , Yuchun Wang
    •  & Shu-Sin Chng

  • Article
    | Open Access

    A key step of drug metabolism in the human body is the uptake into liver cells, which is mediated by transport proteins of the OATP family. Here, authors report cryo-EM structures of two human OATP proteins, providing insight into their function.

    • Anca-Denise Ciută
    • , Kamil Nosol
    •  & Kaspar P. Locher

  • Article
    | Open Access

    The bacterial insertase BAM is a key target for novel antibiotics that are urgently needed. Here, we describe the implementation of an assay that allows screening for BAM inhibitors in the native membrane in high-throughput format.

    • Parthasarathi Rath
    • , Adrian Hermann
    •  & Sebastian Hiller

  • Article
    | Open Access

    ABCG2, an ATP-binding cassette transporter, extrudes hundreds of hydrophilic and hydrophobic compounds from cells, playing roles in xenobiotic clearance or multidrug resistance in cancer. Gose et al provide key insights into ABCG2 substrate selection.

    • Tomoka Gose
    • , Heather M. Aitken
    •  & John D. Schuetz

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