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Article
| Open AccessPhotocrosslinking-induced CRAC channel-like Orai1 activation independent of STIM1
The Ca2+ ion channel Orai1 is crucial in immune cells. Here, the authors applied genetic code expansion to transfer light-sensitivity to the Orai1 channel and achieved precise control over its function.
- Lena Maltan
- , Sarah Weiß
- & Isabella Derler
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Article
| Open AccessPeriodic temperature changes drive the proliferation of self-replicating RNAs in vesicle populations
How primordial cells could achieve inheritance of encapsulated components is still an open question. Here, the authors show that ribozymes can assemble in active forms and replicate in populations of membrane vesicles thanks to freeze-thaw cycles.
- Elia Salibi
- , Benedikt Peter
- & Hannes Mutschler
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Article
| Open AccessStructure and mechanism of a tripartite ATP-independent periplasmic TRAP transporter
Bacteria and archaea use tripartite ATP-independent periplasmic (TRAP) transporters to import essential nutrients. Davies et al. report a high resolution structure of a TRAP and show that it uses an ‘elevator-with-an operator’ mechanism.
- James S. Davies
- , Michael J. Currie
- & Renwick C. J. Dobson
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Article
| Open AccessMembrane phospholipids control gating of the mechanosensitive potassium leak channel TREK1
Tandem pore (K2P) potassium channels set the cellular resting membrane potential in tissues throughout the body. Here, authors show how the composition of phospholipid within the bilayer may directly alter gating in this family of ion channels.
- Philipp A. M. Schmidpeter
- , John T. Petroff II
- & Paul M. Riegelhaupt
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Article
| Open AccessA bivalent remipede toxin promotes calcium release via ryanodine receptor activation
Insect toxins with tandem repeats of neurotoxin domains have been found with enhanced receptor avidity. Here, the authors describe a bivalent toxin from remipede venom that targets ryanodine receptors, a rare target for animal venoms.
- Michael J. Maxwell
- , Chris Thekkedam
- & Mehdi Mobli
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Article
| Open AccessTetraspanin 4 stabilizes membrane swellings and facilitates their maturation into migrasomes
Migrasomes are signaling organelles that form in retraction fibers of migrating cells. Here authors show that migrasomes form by a two-stage process: an initial local membrane swelling matures and is stabilized by recruited tetraspanin proteins.
- Raviv Dharan
- , Yuwei Huang
- & Raya Sorkin
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Article
| Open AccessStructure of human NaV1.6 channel reveals Na+ selectivity and pore blockade by 4,9-anhydro-tetrodotoxin
NaV1.6 channel plays a critical role in neuronal excitability. Here, authors present human NaV1.6 structures in apo and 4,9-anhydro-tetrodotoxin bound forms, which reveal molecular mechanisms of NaV1.6 Na+ conductance and inhibition by the blocker.
- Yue Li
- , Tian Yuan
- & Daohua Jiang
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Article
| Open AccessAnionic phospholipids control mechanisms of GPCR-G protein recognition
In cell membranes, lipids are ubiquitous regulators of protein function. Here, Thakur et al. observe anionic phospholipids impact the conformational dynamics of a class A human GPCR.
- Naveen Thakur
- , Arka P. Ray
- & Matthew T. Eddy
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Article
| Open AccessDifferent pathways for engulfment and endocytosis of liquid droplets by nanovesicles
In this work, the authors investigate on how condensate droplets, arising from liquid-liquid phase separation, can be engulfed by nanovesicles via distinct pathways, leading to different vesicle-droplet morphologies. Two key parameters are the stress asymmetry of the vesicle membrane and the line tension of the contact line between vesicle and droplet.
- Rikhia Ghosh
- , Vahid Satarifard
- & Reinhard Lipowsky
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Article
| Open AccessConformational plasticity of NaK2K and TREK2 potassium channel selectivity filters
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
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Article
| Open AccessThermal fluctuations of the lipid membrane determine particle uptake into Giant Unilamellar Vesicles
Particulates, bacteria and viruses wrap into cell membranes. Here the authors use optical tweezers, particle tracking and mathematical modelling to show that the uptake process into giant vesicles is influenced by thermal membrane fluctuations.
- Yareni A. Ayala
- , Ramin Omidvar
- & Alexander Rohrbach
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Article
| Open AccessBackbone amides are determinants of Cl− selectivity in CLC ion channels
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
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Article
| Open AccessPlanar aggregation of the influenza viral fusion peptide alters membrane structure and hydration, promoting poration
Target membrane poration is a longstanding enigma in virology. Here, authors show that fusion peptides of the influenza virus’ spike protein aggregate, rotate, and tilt in membranes, facilitating peptide-induced poration during viral fusion.
- Amy Rice
- , Sourav Haldar
- & Joshua Zimmerberg
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Article
| Open AccessMembrane curvature governs the distribution of Piezo1 in live cells
This study demonstrates that the curvature of the cell membrane directly regulates the spatial distribution of Piezo1, a widely expressed mechanosensitive ion channel. Piezo1 may flatten upon activation and can mechanically inhibit membrane dynamics
- Shilong Yang
- , Xinwen Miao
- & Zheng Shi
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Article
| Open AccessConformational motions and ligand-binding underlying gating and regulation in IP3R channel
Here authors report cryo-EM structures of IP3R1 which provide atomic details of IP3, Ca2+ and ATP binding. Molecular motions of key domains and sidechains were found to regulate ligand binding and gating, which are validated by functional assays.
- Guizhen Fan
- , Mariah R. Baker
- & Irina I. Serysheva
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Article
| Open AccessGating intermediates reveal inhibitory role of the voltage sensor in a cyclic nucleotide-modulated ion channel
Visualizing conformational changes during ion channel gating is crucial to understand their regulation. Here, Gao et al. capture multiple gating intermediates in a CNG channel as well as subtle, lateral voltage sensor movements necessary for channel opening.
- Xiaolong Gao
- , Philipp A. M. Schmidpeter
- & Crina M. Nimigean
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Article
| Open AccessStructural basis for mechanotransduction in a potassium-dependent mechanosensitive ion channel
Mechanosensitive ion channels mediate biological force sensation, but the underlying mechanism remains poorly understood. Here, authors present the structural basis of mechanotransduction in an ion channel revealed by cryo-electron microscopy.
- Jonathan Mount
- , Grigory Maksaev
- & Peng Yuan
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Article
| Open AccessLipid-mediated prestin organization in outer hair cell membranes and its implications in sound amplification
Prestin, a motor protein, plays a major role in sound amplification. Using molecular dynamics simulations, the authors show that prestin causes membrane deformation patterns thereby achieving a particular lipid-mediated alignment in the membrane.
- Sepehr Dehghani-Ghahnaviyeh
- , Zhiyu Zhao
- & Emad Tajkhorshid
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Article
| Open AccessAn allosteric modulator activates BK channels by perturbing coupling between Ca2+ binding and pore opening
Ca2+ activated BK channels are important for neural and muscle function. Here authors use a compound, BC5, to show that the interface between the cytosolic and voltage sensing domains is a major allosteric pathway for Ca2+ binding to open the channel.
- Guohui Zhang
- , Xianjin Xu
- & Jianmin Cui
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Article
| Open AccessStructural basis for the activation of the lipid scramblase TMEM16F
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
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Article
| Open AccessGi/o protein-coupled receptor inhibition of beta-cell electrical excitability and insulin secretion depends on Na+/K+ ATPase activation
Gi/o protein-coupled receptors (Gi/o-GPCRs) limit β-cell insulin secretion by decreasing Ca2+ entry; however, the underlying mechanism has not been identified. Here, the authors show that Gi/o-GPCRs hyperpolarize mouse and human β-cell membrane potential by activating Na+/K+ATPases.
- Matthew T. Dickerson
- , Prasanna K. Dadi
- & David A. Jacobson
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Article
| Open AccessCryo-EM structures of the translocational binary toxin complex CDTa-bound CDTb-pore from Clostridioides difficile
Binary toxin translocation system consists of an enzymatic subunit and translocation pore. Here, the authors report the high-resolution cryo-EM structure of Clostridioides difficile binary toxin, comprising ADP-ribosyltransferase CDTa bound to the CDTb pore and revealing translocational unfolding of CDTa in the CDTb-pore.
- Akihiro Kawamoto
- , Tomohito Yamada
- & Hideaki Tsuge
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Article
| Open AccessIn vitro assembly, positioning and contraction of a division ring in minimal cells
Constructing a minimal protein machinery for self-division of membrane compartments is a major goal of bottom-up synthetic biology. Here, authors achieved the assembly, placement and onset of contraction of a minimal division ring in lipid vesicles.
- Shunshi Kohyama
- , Adrián Merino-Salomón
- & Petra Schwille
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Article
| Open AccessAssembly of transmembrane pores from mirror-image peptides
Alpha-helix nanopores have a range of potential applications and the inclusion of non-natural amino acids allows for modification. Here, the authors report on the creation of alpha-helix pores using D-amino acids and show the pores formed, have different properties to the L-counterparts and were resistant to proteases.
- Smrithi Krishnan R
- , Kalyanashis Jana
- & Kozhinjampara R. Mahendran
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Article
| Open AccessVisualization of conformational changes and membrane remodeling leading to genome delivery by viral class-II fusion machinery
Membrane fusion is essential for cellular entry of enveloped viruses. Here, authors use time-resolved cryo-electron tomography and subtomogram averaging to capture 3D organization and population evolution of intermediates during membrane fusion of CHIKV, a medically important alphavirus.
- Vidya Mangala Prasad
- , Jelle S. Blijleven
- & Kelly K. Lee
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Article
| Open AccessStructures and gating mechanisms of human bestrophin anion channels
Bestrophin channels are critical for physiology of the eye. Here, authors report cryo-EM structures of human bestrophins in various states at up to 1.8 Å resolution, revealing paralog-specific features that underlie molecular mechanisms of permeation.
- Aaron P. Owji
- , Jiali Wang
- & Tingting Yang
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Article
| Open AccessStructural and electrophysiological basis for the modulation of KCNQ1 channel currents by ML277
KCNQ1 channels are active in heart, brain and gut. Functional loss causes epilepsy and sudden arrhythmic death. Here, authors describe a key activator drug binding site, explaining isoform and drug selectivity, and point the way for new drug design.
- Katrien Willegems
- , Jodene Eldstrom
- & David Fedida
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Article
| Open AccessKir2.1-mediated membrane potential promotes nutrient acquisition and inflammation through regulation of nutrient transporters
Potassium channels and membrane potential may influence macrophage function during inflammation. Here the authors show that the Kir2.1 potassium channel affects macrophage metabolism by altering cell surface retention of nutrient transporters and subsequently regulates inflammatory disease responses.
- Weiwei Yu
- , Zhen Wang
- & Di Wang
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Article
| Open AccessMembrane curvature regulates the spatial distribution of bulky glycoproteins
MUC1 is a heavily glycosylated protein on the cell surface. Here the authors show that MUC1 prefers negative over positive membrane curvature due to its bulky size, enabling MUC1 to avoid endocytosis and surface removal based on curvature preference.
- Chih-Hao Lu
- , Kayvon Pedram
- & Bianxiao Cui
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Article
| Open AccessP-selectin mobility undergoes a sol-gel transition as it diffuses from exocytosis sites into the cell membrane
P-selectin recruits leucocytes to regions of blood vessel damage. Using single molecule imaging, we find newly secreted P-selectin spreads rapidly across the plasma membrane and then becomes immobilized and better-suited to leucocyte capture.
- Nicola Hellen
- , Gregory I. Mashanov
- & Tom Carter
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Article
| Open AccessInhibition mechanism of the chloride channel TMEM16A by the pore blocker 1PBC
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
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Article
| Open AccessN-type fast inactivation of a eukaryotic voltage-gated sodium channel
Voltage-gated sodium channels mediate electrical signaling. Here, authors report the cryo-EM structure of NaVEh from the marine plant Emiliania huxleyi, revealing an unexpected mechanism of N-type fast inactivation.
- Jiangtao Zhang
- , Yiqiang Shi
- & Daohua Jiang
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Article
| Open AccessStructural anatomy of Protein Kinase C C1 domain interactions with diacylglycerol and other agonists
Protein kinase Cs (PKCs) define a central DAG-sensing node in intracellular phosphoinositide signaling pathways that regulate cell growth, differentiation, apoptosis, and motility. The structures of PKC C1 domain complexes with DAG and 4 agonists reveal the molecular basis of ligand recognition and capture.
- Sachin S. Katti
- , Inna V. Krieger
- & Tatyana I. Igumenova
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Article
| Open AccessSnf7 spirals sense and alter membrane curvature
Snf7 is the major component of the ESCRTIII membrane deformation system. Here, the authors used high-speed AFM to study Snf7 on nano-patterned and soft supports and show that loaded Snf7 spiral springs are curvature sensitive and deform membranes.
- Nebojsa Jukic
- , Alma P. Perrino
- & Simon Scheuring
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Article
| Open AccessExploration of the dynamic interplay between lipids and membrane proteins by hydrostatic pressure
Direct information on the dynamic interplay between membrane proteins and lipids is scarce. Here the authors report a detailed description of these close relationships by combining lipid nanodiscs and high-pressure NMR. They report the link between pressure and lipid compositions to the conformational landscape of the β-barrel OmpX and the α-helical BLT2 G Protein-Coupled Receptor in nanodiscs.
- Alexandre Pozza
- , François Giraud
- & Laurent J. Catoire
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Article
| Open AccessA distinct mechanism of C-type inactivation in the Kv-like KcsA mutant E71V
Constriction of the selectivity filter is assumed to be a hallmark of C-type inactivation in K+ channels. Using different high-resolution methods, this study shows a distinct C-type inactivation mechanism in a KcsA mutant that emulates Kv-channels.
- Ahmed Rohaim
- , Bram J. A. Vermeulen
- & Markus Weingarth
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Article
| Open AccessIntrinsically disordered intracellular domains control key features of the mechanically-gated ion channel PIEZO2
A key question in mechanobiology is how mechanical forces are transmitted to PIEZO ion channels. Here, Verkest et al. identify an intracellular channel domain that is required for the activation of PIEZO2 by cytoskeleton-transmitted forces.
- Clement Verkest
- , Irina Schaefer
- & Stefan G. Lechner
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Article
| Open AccessStructural basis for modulation of human NaV1.3 by clinical drug and selective antagonist
NaV1.3 is involved in neuronal development, hormone secretion and pain perception. Here, the authors elucidate the molecular mechanism for modulation of NaV1.3 by a site-2 neurotoxin bulleyaconitine A and a subtype selective antagonist ICA121431.
- Xiaojing Li
- , Feng Xu
- & Daohua Jiang
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Article
| Open AccessHigh-pH structure of EmrE reveals the mechanism of proton-coupled substrate transport
EmrE transporter effluxes cationic substrates across lipid membranes in a pH-coupled manner. Here, the authors solve the structure of ligand-bound EmrE at high pH by NMR, with insights into the transport mechanism.
- Alexander A. Shcherbakov
- , Peyton J. Spreacker
- & Mei Hong
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Article
| Open AccessStructural insights into the Venus flytrap mechanosensitive ion channel Flycatcher1
Flycatcher1 (FLYC1) is a candidate mechanosensitive channel involved in Venus flytrap touch-induced prey capture. Here, the authors report structural and functional details of FLYC1, with insights into gating conformational transitions.
- Sebastian Jojoa-Cruz
- , Kei Saotome
- & Andrew B. Ward
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Article
| Open AccessHyperuniformity and phase enrichment in vortex and rotor assemblies
Rotor-like dynamics is observed in many natural systems, from the rotor proteins in cellular membranes to atmospheric models. Here, the authors uncover geometrical conservation laws that limit distribution of driven rotors in a membrane or a soap film and allow to predict their structural states.
- Naomi Oppenheimer
- , David B. Stein
- & Michael J. Shelley
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Article
| Open AccessA method to construct the dynamic landscape of a bio-membrane with experiment and simulation
The authors present a strategy to construct dynamic biomolecular landscapes. Here, they derive a quantitative description of the distribution timescales and amplitudes of reorientational motion of POPC membranes from the combination of NMR relaxation data and frame analysis of MD simulations.
- Albert A. Smith
- , Alexander Vogel
- & Daniel Huster
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Article
| Open AccessSingle molecule kinetics of bacteriorhodopsin by HS-AFM
Here, the authors use high-speed atomic force microscopy (HS-AFM) methods to characterize the single molecule kinetics of wild-type bacteriorhodopsin (bR) with millisecond temporal resolution, providing new insights into the bR conformational cycle.
- Alma P. Perrino
- , Atsushi Miyagi
- & Simon Scheuring
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Article
| Open AccessMonitoring the binding and insertion of a single transmembrane protein by an insertase
The insertion and folding nascent or fully synthesized polypeptides into membranes is assisted by insertases. Here, the authors use a range of biophysical approaches to provide molecular details of how the transmembrane insertase YidC facilitates the insertion a protein into a phospholipid membrane.
- Pawel R. Laskowski
- , Kristyna Pluhackova
- & Daniel J. Müller
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Article
| Open AccessMolecular architecture of black widow spider neurotoxins
The venom of Latrodectus spiders contains seven Latrotoxins (LaTXs), among them α-latrocrustatoxin (LCT) and δ- latroinsectotoxins δ-LIT. LaTXs bind to specific receptors on the surface of neuronal cells and target the molecular exocytosis machinery. Here, the authors present the cryo-EM structure of the α-LCT monomer and the δ-LIT dimer, which reveal that LaTXs are organized in four domains and they discuss the potential oligomerisation mechanism that takes place before LaTXs membrane insertion. Both recombinant α-LCT and δ-LIT form channels in artificial membrane bilayers, that are stabilized by Ca2+ ions.
- Minghao Chen
- , Daniel Blum
- & Christos Gatsogiannis
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Article
| Open AccessFree energies of membrane stalk formation from a lipidomics perspective
Fusion of cellular membranes begins with the formation of a stalk. Here, the authors develop a computationally efficient method for coarse-grained simulations of stalk formation and apply this approach to comprehensively analyse how stalk formation is influenced by the membrane lipid composition.
- Chetan S. Poojari
- , Katharina C. Scherer
- & Jochen S. Hub
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Article
| Open AccessDynamic mechanochemical feedback between curved membranes and BAR protein self-organization
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
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Article
| Open AccessLysine acetylation regulates the interaction between proteins and membranes
Lysine acetylation regulates the function of soluble proteins in vivo, yet it remains largely unexplored whether lysine acetylation regulates the function of membrane proteins. Here, the authors map lysine acetylation predominantly in membrane-interaction regions in peripheral membrane proteins and show with three candidate proteins how lysine acetylation is a regulator of membrane protein function.
- Alan K. Okada
- , Kazuki Teranishi
- & Ralf Langen
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Article
| Open AccessStructural basis of human ghrelin receptor signaling by ghrelin and the synthetic agonist ibutamoren
Ghrelin is a central orexigenic peptide hormone in human energy homeostasis that is also known as ‘hunger hormone’ and signals through its GPCR, GHSR. Here, the authors present the cryo-EM structures of the human GHSR-Gi signaling complex with bound ghrelin and the synthetic non-peptide agonist ibutamoren that are of interest for drug design.
- Heng Liu
- , Dapeng Sun
- & Cheng Zhang