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Structural basis of lipid head group entry to the Kennedy pathway by FLVCR1
A structural, biochemical and metabolomic analysis reveals the mechanistic basis for transport of extracellular choline and ethanolamine into cells by the human transport protein FLVCR1.
- Yeeun Son
- , Timothy C. Kenny
- & Richard K. Hite
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Review Article |
Ion and lipid orchestration of secondary active transport
This Review describes the various mechanisms of ion-coupled transport across membranes and how the activities of transporter proteins are modulated by the composition of the lipid bilayer.
- David Drew
- & Olga Boudker
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Article |
Transport and inhibition mechanisms of human VMAT2
Structures of human vesicular monoamine transporter 2 in complexes with serotonin and three clinical drugs provide insights into the structural basis for serotonin transport and inhibition of transporter activity by the drugs.
- Di Wu
- , Qihao Chen
- & Daohua Jiang
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Article
| Open AccessStructure and electromechanical coupling of a voltage-gated Na+/H+ exchanger
Upon hyperpolarization, the S4 voltage-sensing segment of sea urchin SLC9C1 moves down, removing inhibition caused by an intracellular helix and enabling Na+/H+ exchange, leading to pH-dependent activation of sAC and sperm chemotaxis.
- Hyunku Yeo
- , Ved Mehta
- & David Drew
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Article |
Outer membrane utilisomes mediate glycan uptake in gut Bacteroidetes
A structural and functional analysis of the systems involved in oligosaccharide uptake in gut Bacteroidetes describes multicomponent complexes termed utilisomes that include pre-processing and transport subunits.
- Joshua B. R. White
- , Augustinas Silale
- & Neil A. Ranson
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Article
| Open AccessVisualizing the disordered nuclear transport machinery in situ
Previously shown as a 60-nm hole in the nuclear pore complex, the transport machinery by FG-nucleoporins is mapped.
- Miao Yu
- , Maziar Heidari
- & Edward A. Lemke
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Article |
Structural basis of sensory receptor evolution in octopus
Cryo-electron microscopy analyses reveal adaptations that facilitate the octopus chemotactile receptor’s evolutionary transition from an ancestral role in neurotransmission to detecting greasy environmental agonists for ‘taste by touch’ sensory behaviour.
- Corey A. H. Allard
- , Guipeun Kang
- & Nicholas W. Bellono
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Article |
Sensory specializations drive octopus and squid behaviour
Octopus and squid use cephalopod-specific chemotactile receptors to sense their respective marine environments, but structural adaptations in these receptors support the sensation of specific molecules suited to distinct physiological roles.
- Guipeun Kang
- , Corey A. H. Allard
- & Ryan E. Hibbs
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Article |
Structure and thiazide inhibition mechanism of the human Na–Cl cotransporter
Using cryo-electron microscopy, the structures of human Na–Cl cotransporter are determined alone and in complex with a thiazide diuretic.
- Minrui Fan
- , Jianxiu Zhang
- & Liang Feng
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Article |
Regulation of the mammalian-brain V-ATPase through ultraslow mode-switching
Single-molecule measurements of synaptic vesicles show that V-ATPases do not pump continuously in time but instead stochastically switch between ultralong-lived proton-pumping, inactive and proton-leaky modes.
- Eleftherios Kosmidis
- , Christopher G. Shuttle
- & Dimitrios Stamou
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Article |
Methotrexate recognition by the human reduced folate carrier SLC19A1
Cryo-EM structures provide insight into how the antifolate methotrexate, a chemotherapy drug, is recognized by the reduced folate carrier.
- Nicholas J. Wright
- , Justin G. Fedor
- & Seok-Yong Lee
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Article |
Structures and mechanisms of the Arabidopsis auxin transporter PIN3
Arabidopsis thaliana PIN3 structures reveal the molecular mechanisms of the transport of indole-3-acetic acid and the inhibition of polar auxin transport by N-1-naphthylphthalamic acid.
- Nannan Su
- , Aiqin Zhu
- & Jiangtao Guo
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Article
| Open AccessStructural basis of sodium-dependent bile salt uptake into the liver
Structural studies of human Na+–taurocholate co-transporting polypeptide in complex with nanobodies reveal mechanisms for bile salts transport and HBV recognition involving an open-pore intermediate state.
- Kapil Goutam
- , Francesco S. Ielasi
- & Nicolas Reyes
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Article
| Open AccessOpening of glutamate receptor channel to subconductance levels
Cryo-EM structures of AMPA receptor with the subunit γ2 in non-desensitizing conditions at low glutamate concentrations disprove the one-to-one link between the number of glutamate-bound subunits and ionotropic glutamate receptor conductance.
- Maria V. Yelshanskaya
- , Dhilon S. Patel
- & Alexander I. Sobolevsky
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Article |
Structure and mechanism of the SGLT family of glucose transporters
Cryo-electron microscopy structures of the sodium–glucose cotransporter SGLT1 and a related transporter SMCT1 define the architecture of this protein family and provide insights into substrate binding and transport function.
- Lei Han
- , Qianhui Qu
- & Liang Feng
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Article |
Dispatched uses Na+ flux to power release of lipid-modified Hedgehog
Cryo-electron microscopy studies show that dynamic coordination of Na+ in the ion channel of Dispatched homologue 1 and the transmembrane Na+ gradient have key roles in exporting lipid-modified Hedgehog protein signal.
- Qianqian Wang
- , Daniel E. Asarnow
- & Philip A. Beachy
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Article |
Structure of a mammalian sperm cation channel complex
A structure of the sperm-specific CatSper complex features a number of additional components; together, these components and the CatSper complex are termed the CatSpermasome.
- Shiyi Lin
- , Meng Ke
- & Jianping Wu
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Article |
Structural basis of omega-3 fatty acid transport across the blood–brain barrier
Cryo-electron microscopy and molecular dynamics simulations reveal how MFSD2A transports essential omega-3 fatty acids across the blood–brain and blood–retina barriers as lysolipids.
- Rosemary J. Cater
- , Geok Lin Chua
- & Filippo Mancia
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Article |
Structural basis of antifolate recognition and transport by PCFT
Cryo-electron microscopy structures of PCFT in a substrate-free state and bound to the antifolate drug pemetrexed provide insights into how this protein recognizes folates and mediates their transport into cells.
- Joanne L. Parker
- , Justin C. Deme
- & Simon Newstead
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Article |
Structure and inhibition mechanism of the human citrate transporter NaCT
Structures of the human sodium-dependent citrate transporter NaCT in complexes with citrate or a small-molecule inhibitor reveal how the inhibitor—which binds to the same site as citrate—arrests the transport cycle of NaCT.
- David B. Sauer
- , Jinmei Song
- & Da-Neng Wang
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Article |
Glutamate transporters have a chloride channel with two hydrophobic gates
Glutamate transporters conduct chloride ions through an aqueous channel with hydrophobic gates that forms during the glutamate transport cycle.
- Ichia Chen
- , Shashank Pant
- & Renae M. Ryan
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Article |
Cryo-EM structures of apo and antagonist-bound human Cav3.1
Partial structures are reported for Cav3.1 both on its own and in complex with a phase II drug candidate for seizure and neuropathic pain; this presents the overall architecture of T-type Ca2+ channels, insights into their gating and permeation mechanisms, and how they are modulated by small-molecule blockers.
- Yanyu Zhao
- , Gaoxingyu Huang
- & Nieng Yan
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Article |
Structure and mechanism of the cation–chloride cotransporter NKCC1
The cryo-EM structure of the zebrafish cation–chloride cotransporter NKCC1 reveals the domain organization, ion translocation pathway, ion-binding sites and key residues for binding activity, providing insights into the activity of this family of transporter proteins with key roles in physiology.
- Thomas A. Chew
- , Benjamin J. Orlando
- & Liang Feng
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Article |
Modulation of cardiac ryanodine receptor 2 by calmodulin
The regulatory mechanism through which ryanodine receptor 2 is modulated by calmodulin is revealed through structural determination of ryanodine receptor 2 under eight conditions.
- Deshun Gong
- , Ximin Chi
- & Nieng Yan
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Letter |
Conformational transitions of the serotonin 5-HT3 receptor
Cryo-electron microscopy of the serotonin 5-HT3 receptor in complex with various ligands yields four distinct structures, capturing serotonin binding in detail and increasing understanding of the gating mechanism of the receptor.
- Lucie Polovinkin
- , Ghérici Hassaine
- & Hugues Nury
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Article |
Cryo-EM structure of a fungal mitochondrial calcium uniporter
A cryo-electron microscopy structure of fungal mitochondrial calcium uniporter shows that the channel is tetrameric and sheds light on channel assembly and function.
- Nam X. Nguyen
- , Jean-Paul Armache
- & Youxing Jiang
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Article |
Structure of a volume-regulated anion channel of the LRRC8 family
The structure of a homomeric channel of subunit A of leucine-rich repeat-containing protein 8 (LRRC8) determined by cryo-electron microscopy and X-ray crystallography reveals the basis for anion selectivity.
- Dawid Deneka
- , Marta Sawicka
- & Raimund Dutzler
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Letter |
Gating mechanisms of acid-sensing ion channels
X-ray and cryo-electron microscopy structures of the acid-sensing ion channel ASIC1a reveal the molecular mechanisms of channel gating and desensitization.
- Nate Yoder
- , Craig Yoshioka
- & Eric Gouaux
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Letter |
Opening of the human epithelial calcium channel TRPV6
The cryo-electron microscopy structure of the calcium channel TRPV6 in its open and closed states demonstrates a novel gating mechanism involving an alanine hinge.
- Luke L. McGoldrick
- , Appu K. Singh
- & Alexander I. Sobolevsky
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Letter |
Cryo-electron microscopy structure of the lysosomal calcium-permeable channel TRPML3
A cryo-electron microscopy structure shows that the mucolipin domain of the lysosomal calcium channel TRPML3 binds phosphatidylinositol-3,5-bisphosphate and gates the channel.
- Marscha Hirschi
- , Mark A. Herzik Jr
- & Seok-Yong Lee
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Letter |
Structure of mammalian endolysosomal TRPML1 channel in nanodiscs
The structure of mouse transient receptor potential mucolipin 1 (TRPML1), a cation channel located within endosomal and lysosomal membranes, is resolved using single-particle electron cryo-microscopy.
- Qingfeng Chen
- , Ji She
- & Youxing Jiang
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Letter |
The lysosomal potassium channel TMEM175 adopts a novel tetrameric architecture
The lysosomal potassium channel TMEM175 has a tetrameric structure unlike that of the canonical potassium channels, with an hourglass-shaped pore in which isoleucine residues have a key role in channel selectivity.
- Changkeun Lee
- , Jiangtao Guo
- & Youxing Jiang
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Article |
Structure and allosteric inhibition of excitatory amino acid transporter 1
High-resolution structures of the thermostabilized human excitatory amino acid transporter EAAT1, alone or in association with its substrate or small molecule inhibitors, reveal architectural features of human SLC1 transporters and an allosteric mechanism of inhibition.
- Juan C. Canul-Tec
- , Reda Assal
- & Nicolas Reyes
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Article |
Visualizing multistep elevator-like transitions of a nucleoside transporter
Multiple crystallographic structures of a concentrative nucleoside transporter show how it uses an ‘elevator’ mechanism to move its transport domain across the membrane.
- Marscha Hirschi
- , Zachary Lee Johnson
- & Seok-Yong Lee
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Letter |
Energy transduction and alternating access of the mammalian ABC transporter P-glycoprotein
Double electron–electron resonance and computer simulations are used to describe conformational dynamics in the ATP-binding cassette transporter Pgp, which has an important role in the clearance of xenobiotics and cancer resistance to chemotherapy.
- Brandy Verhalen
- , Reza Dastvan
- & Hassane S. Mchaourab
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Letter |
Structural basis of the alternating-access mechanism in a bile acid transporter
Inhibitors of the bile acid transporter ASBT may be useful therapeutics for treating hypercholesterolaemia and type 2 diabetes; here, two X-ray crystal structures of an ASBT homologue from Yersinia frederiksenii are solved.
- Xiaoming Zhou
- , Elena J. Levin
- & Ming Zhou
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Letter |
A two-domain elevator mechanism for sodium/proton antiport
The X-ray crystal structure of NapA, a Na+/H+ antiporter from Thermus thermophilus, in an active, outward-facing state is reported; comparisons to the structure of a related transporter in a low pH/inactivated, inward-facing state show the conformational changes that occur when the membrane protein moves from an inward-facing to an outward-facing state, suggesting that Na+/H+ antiporters operate by a two-domain rocking bundle model.
- Chiara Lee
- , Hae Joo Kang
- & David Drew
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Article |
Gating of the TrkH ion channel by its associated RCK protein TrkA
Here it is shown that ion flux through the TrkH–TrkA complex is upregulated by ATP and downregulated by ADP; solving the X-ray crystal structures of the tetrameric TrkA ring in the absence and presence of TrkH suggests a mechanism by which ATP-induced conformational changes in TrkA augment the activity of TrkH.
- Yu Cao
- , Yaping Pan
- & Ming Zhou
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Letter |
Gated regulation of CRAC channel ion selectivity by STIM1
STIM1-mediated gating of CRAC channels occurs through a mechanism in which ion selectivity and gating are closely coupled, and the residue V102 is identified as a candidate for the channel gate.
- Beth A. McNally
- , Agila Somasundaram
- & Murali Prakriya
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Letter |
Preserving the membrane barrier for small molecules during bacterial protein translocation
- Eunyong Park
- & Tom A. Rapoport