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Letter |
Structure of the human LAT1–4F2hc heteromeric amino acid transporter complex
The cryo-EM structure of the LAT1–4F2hc complex, a heteromeric amino acid transporter, is characterized, providing insights into its function and the mechanisms through which mutations of this complex could cause disease.
- Renhong Yan
- , Xin Zhao
- & Qiang Zhou
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Article |
Structural insights into the activation of metabotropic glutamate receptors
The activation mechanism of metabotropic glutamate receptor subtype 5, a member of the family C G-protein-coupled receptors, is characterized by a combination of cryo-electron microscopy, crystallography and signalling studies.
- Antoine Koehl
- , Hongli Hu
- & Brian K. Kobilka
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Letter |
SETD3 is an actin histidine methyltransferase that prevents primary dystocia
SETD3 methylates mammalian actin at His73, and SETD3 deficiency impairs stimulus-induced contraction in primary human uterine smooth muscle cells and leads to maternal dystocia in mice.
- Alex W. Wilkinson
- , Jonathan Diep
- & Or Gozani
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Letter |
Cryo-EM structures of a human ABCG2 mutant trapped in ATP-bound and substrate-bound states
Cryo-electron microscopy structures of the ABCG2 protein in ATP- and substrate-bound states reveal the location of substrate binding, conformational changes required for substrate translocation and how inhibitors might be distinguished from substrates.
- Ioannis Manolaridis
- , Scott M. Jackson
- & Kaspar P. Locher
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Letter |
A protein functionalization platform based on selective reactions at methionine residues
This methionine-selective functionalization strategy uses hypervalent iodine reagents to introduce new groups via the formation of a sulfonium intermediate, which can then undergo further visible-light-mediated reactions to form a diverse range of protein conjugates.
- Michael T. Taylor
- , Jennifer E. Nelson
- & Matthew J. Gaunt
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Article |
The interaction landscape between transcription factors and the nucleosome
A method for systematically exploring interactions between the nucleosome and transcription factors identifies five major interaction patterns.
- Fangjie Zhu
- , Lucas Farnung
- & Jussi Taipale
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Letter |
mRNA circularization by METTL3–eIF3h enhances translation and promotes oncogenesis
METTL3, the enzyme responsible for m6A modification, influences translation by interacting with eIF3h to mediate looping between the regions near the stop codon and 5′ cap of mRNA.
- Junho Choe
- , Shuibin Lin
- & Richard I. Gregory
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Article |
De novo design of a fluorescence-activating β-barrel
The elucidation of general principles for designing β-barrels enables the de novo creation of fluorescent proteins.
- Jiayi Dou
- , Anastassia A. Vorobieva
- & David Baker
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Letter |
The NORAD lncRNA assembles a topoisomerase complex critical for genome stability
The long non-coding RNA NORAD interacts with proteins involved in DNA replication and repair, and controls the ability of RBMX to form a ribonucleoprotein complex that helps to maintain genomic stability.
- Mathias Munschauer
- , Celina T. Nguyen
- & Eric S. Lander
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Article |
Cryo-EM structures of fungal and metazoan mitochondrial calcium uniporters
Structures of the mitochondrial calcium uniporter from fungal and metazoan organisms reveal a tetrameric architecture and shed light on the function of the channel.
- Rozbeh Baradaran
- , Chongyuan Wang
- & Stephen Barstow Long
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Article |
Structure of the origin recognition complex bound to DNA replication origin
The cryo-EM structure of the yeast origin recognition complex (ORC) bound to a 72-base-pair origin DNA sequence provides insights into the basis of the origin selection mechanism.
- Ningning Li
- , Wai Hei Lam
- & Bik-Kwoon Tye
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Letter |
Cryo-EM structure of the serotonin 5-HT1B receptor coupled to heterotrimeric Go
The high-resolution structure of the serotonin 5-HT1B receptor in complex with the agonist donitriptan and a Go heterotrimer highlights features that may underlie the specificity of receptor–G-protein coupling and kinetics of signalling.
- Javier García-Nafría
- , Rony Nehmé
- & Christopher G. Tate
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Article |
Structure of the adenosine-bound human adenosine A1 receptor–Gi complex
The cryo-electron microscopy structure of the human adenosine A1 receptor in complex with adenosine and heterotrimeric Gi2 protein provides molecular insights into receptor and G-protein selectivity.
- Christopher J. Draper-Joyce
- , Maryam Khoshouei
- & Arthur Christopoulos
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Article |
Cryo-EM structure of human rhodopsin bound to an inhibitory G protein
The cryo-electron microscopy structure of human rhodopsin bound to the inhibitory Gi protein-coupled receptor provides insights into ligand–receptor–G-protein interactions.
- Yanyong Kang
- , Oleg Kuybeda
- & H. Eric Xu
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Letter |
Structure of the alternative complex III in a supercomplex with cytochrome oxidase
The structure of alternative complex III, a key enzyme in the bacterial electron transport chain, is reported both alone and as a supercomplex with an aa3-type cytochrome c oxidase.
- Chang Sun
- , Samir Benlekbir
- & Robert B. Gennis
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Letter |
Structural basis of ligand binding modes at the neuropeptide Y Y1 receptor
Crystal structures of the neuropeptide Y1 receptor in complex with two distinct antagonists combined with NMR, molecular docking and mutagenesis studies inform a proposed model for receptor–agonist binding.
- Zhenlin Yang
- , Shuo Han
- & Beili Wu
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Article |
Crystal structures of the gastric proton pump
Crystal structures of the gastric proton pump in complex with two inhibitory drugs reveal the mechanism that generates the steep acidic gradient across the membranes of parietal cells.
- Kazuhiro Abe
- , Katsumasa Irie
- & Yoshinori Fujiyoshi
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Letter |
The cryo-electron microscopy structure of huntingtin
The structure of huntingtin in complex with an interactor is determined to an overall resolution of 4 Å, paving the way for improved understanding of the cellular functions of this protein.
- Qiang Guo
- , Bin Huang
- & Stefan Kochanek
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Article |
Cryo-EM shows how dynactin recruits two dyneins for faster movement
Cryo-electron microscopy and single-molecule studies reveal that the adaptors BICDR1 and HOOK3 recruit two dynein molecules to dynactin and thereby increase the force and speed of the dynein–dynactin microtubule motor.
- Linas Urnavicius
- , Clinton K. Lau
- & Andrew P. Carter
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Letter |
A semi-synthetic organism that stores and retrieves increased genetic information
A modified Escherichia coli is used to demonstrate that semi-synthetic organisms can use non-natural hydrophobic base pairs to genetically encode for the incorporation of non-canonical amino acids into proteins.
- Yorke Zhang
- , Jerod L. Ptacin
- & Floyd E. Romesberg
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Article |
Massively parallel de novo protein design for targeted therapeutics
A massively parallel computational and experimental approach for de novo designing and screening small hyperstable proteins targeting influenza haemagglutinin and botulinum neurotoxin B identifies new therapeutic candidates more robust than traditional antibody therapies.
- Aaron Chevalier
- , Daniel-Adriano Silva
- & David Baker
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Letter |
Alternative evolutionary histories in the sequence space of an ancient protein
Combining ancestral protein reconstruction with deep mutational scanning to characterize alternative histories in the sequence space around an ancient transcription factor reveals hundreds of alternative protein sequences that use diverse biochemical mechanisms to perform the derived function at least as well as the historical outcome.
- Tyler N. Starr
- , Lora K. Picton
- & Joseph W. Thornton
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Letter |
How type II CRISPR–Cas establish immunity through Cas1–Cas2-mediated spacer integration
Several structures of the Enteroccocus faecalis Cas1–Cas2 proteins are solved, and help to define the spacer integration mechanisms of type II CRISPR systems.
- Yibei Xiao
- , Sherwin Ng
- & Ailong Ke
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Letter |
Structural insights into ligand recognition by the lysophosphatidic acid receptor LPA6
Determination of the crystal structure of the zebrafish LPA6 receptor shows that the lipid ligand binds to an unusual ligand-binding pocket in the receptor that is laterally accessible through the membrane.
- Reiya Taniguchi
- , Asuka Inoue
- & Osamu Nureki
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Letter |
Crystal structure of the potassium-importing KdpFABC membrane complex
The crystal structure of the bacterial potassium import complex KdpFABC shows how ATP hydrolysis is coupled to potassium transport to maintain cellular homeostasis under low potassium conditions.
- Ching-Shin Huang
- , Bjørn Panyella Pedersen
- & David L. Stokes
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Article |
Structure of the human multidrug transporter ABCG2
The structure of human ABCG2 bound to an inhibitory antibody using cryo-electron microscopy, representing the first high-resolution structural data of a human multidrug transporter.
- Nicholas M. I. Taylor
- , Ioannis Manolaridis
- & Kaspar P. Locher
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Article |
Cryo-EM structure of the activated GLP-1 receptor in complex with a G protein
The structure of the GLP-1 receptor complexed with its ligand offers insight into the mechanism of class B G-protein-coupled receptor activation.
- Yan Zhang
- , Bingfa Sun
- & Georgios Skiniotis
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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 |
Electric-field-stimulated protein mechanics
A new method in which strong electric fields are applied to a protein crystal while collecting time-resolved X-ray diffraction patterns is able to follow the mechanical motions of all the constituent atoms, with implications for molecular biology and drug discovery.
- Doeke R. Hekstra
- , K. Ian White
- & Rama Ranganathan
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Review Article |
Organization and functions of mGlu and GABAB receptor complexes
This Review discusses current knowledge of the structure, function and interactions of the metabotropic glutamate and GABAB receptors and the potential to target receptor subunits for future therapeutic intervention in neurological and mental health disorders.
- Jean-Philippe Pin
- & Bernhard Bettler
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Letter |
High-resolution crystal structure of the human CB1 cannabinoid receptor
The authors report a 2.6 Å resolution crystal structure of the human CB1 cannabinoid receptor trapped in the inactive conformation and bound to the antagonist taranabant.
- Zhenhua Shao
- , Jie Yin
- & Daniel M. Rosenbaum
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Article |
The pathway to GTPase activation of elongation factor SelB on the ribosome
The structures of several states on the pathway of SelB-mediated delivery of selenocysteine-specific tRNA to the ribosome in Escherichia coli reveal the mechanism of UGA stop codon recoding to selenocysteine and show how codon recognition triggers activation of translational GTPases.
- Niels Fischer
- , Piotr Neumann
- & Holger Stark
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Letter |
Atomic model for the membrane-embedded VO motor of a eukaryotic V-ATPase
The structure of the VO subcomplex of yeast V-ATPase, solved by electron cryomicroscopy, reveals a new subunit and suggests a mechanism for the translocation of protons across membranes.
- Mohammad T. Mazhab-Jafari
- , Alexis Rohou
- & John L. Rubinstein
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Article |
Arginine phosphorylation marks proteins for degradation by a Clp protease
In Gram-positive bacteria, arginine phosphorylation by the McsB kinase functions as a general post-translational marker for Clp-mediated proteolysis.
- Débora Broch Trentini
- , Marcin Józef Suskiewicz
- & Tim Clausen
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Article |
The architecture of respiratory supercomplexes
Respirasomes are supercomplexes of mitochondrial electron transport chain complexes that are responsible for cellular respiration and energy production; cryo-electron microscopy structures of mammalian (sheep) respirasomes are presented.
- James A. Letts
- , Karol Fiedorczuk
- & Leonid A. Sazanov
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Letter |
Accessory subunits are integral for assembly and function of human mitochondrial complex I
Gene-editing technology and large-scale proteomics are used to provide insights into the modular assembly of the human mitochondrial respiratory chain complex I, as well as identifying new assembly factors.
- David A. Stroud
- , Elliot E. Surgenor
- & Michael T. Ryan
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Letter |
Acetylation-regulated interaction between p53 and SET reveals a widespread regulatory mode
The acidic domain of SET binds and represses unacetylated p53, but this interaction is prevented by cellular-stress-induced p53 CTD acetylation.
- Donglai Wang
- , Ning Kon
- & Wei Gu
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Article |
Activation mechanism of endothelin ETB receptor by endothelin-1
The X-ray crystal structures of human endothelin type B receptor in the ligand-free form and in complex with the endogenous agonist endothelin-1.
- Wataru Shihoya
- , Tomohiro Nishizawa
- & Tomoko Doi
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Letter |
Insights from biochemical reconstitution into the architecture of human kinetochores
Biochemical reconstitution of a synthetic human kinetochore with 21 protein subunits and centromeric nucleosomal DNA unveils fundamental principles of kinetochore organization and function.
- John R. Weir
- , Alex C. Faesen
- & Andrea Musacchio
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Article |
Structure-based discovery of opioid analgesics with reduced side effects
Computational docking to the the μ-opioid-receptor identifies PZM21, a novel selective biased agonist that generates substantial affective analgesia in mice without altering respiration or inducing drug reinforcement.
- Aashish Manglik
- , Henry Lin
- & Brian K. Shoichet
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Letter |
Diverse activation pathways in class A GPCRs converge near the G-protein-coupling region
A highly conserved rearrangement of residue contacts functions as a common step in the activation pathways of diverse G-protein-coupled receptors.
- A. J. Venkatakrishnan
- , Xavier Deupi
- & M. Madan Babu
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Letter |
HIV-1 uses dynamic capsid pores to import nucleotides and fuel encapsidated DNA synthesis
Size-selective pores in the HIV-1 capsid hexamer recruit nucleotides, thereby allowing reverse transcription to take place inside the capsid.
- David A. Jacques
- , William A. McEwan
- & Leo C. James
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Article |
Capturing a substrate in an activated RING E3/E2–SUMO complex
A new method based on protein engineering to trap an intact complex between Siz1, SUMO-bound E2, and PCNA for structure determination.
- Frederick C. Streich Jr
- & Christopher D. Lima
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Letter |
Structure of mammalian respiratory complex I
Electron cryomicroscopy structures are provided for all core and supernumerary protein subunits of mammalian complex I, a 45-subunit enzyme that powers eukaryotic respiration.
- Jiapeng Zhu
- , Kutti R. Vinothkumar
- & Judy Hirst
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Letter |
Global profiling of SRP interaction with nascent polypeptides
Here, the selection of substrates by the protein–RNA complex known as the signal recognition particle (SRP) is investigated in the bacterium Escherichia coli, revealing that the SRP has a strong preference for hydrophobic transmembrane domains of inner membrane proteins.
- Daniela Schibich
- , Felix Gloge
- & Günter Kramer
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Letter |
The structural basis of modified nucleosome recognition by 53BP1
A cryo-electron microscopy structure of the DNA damage repair protein 53BP1 bound to a nucleosome illuminates the way 53BP1 recognizes two types of histone modifications (a methyl group and a ubiquitin moiety), and provides insight into the highly specified recognition and recruitment of 53BP1 to modified chromatin.
- Marcus D. Wilson
- , Samir Benlekbir
- & Daniel Durocher
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Letter |
Structure of the adenosine A2A receptor bound to an engineered G protein
An engineered G protein is used to bind to and stabilize the active conformation of the adenosine A2A receptor, enabling the acquisition of an X-ray crystal structure of this GPCR in an active state.
- Byron Carpenter
- , Rony Nehmé
- & Christopher G. Tate
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Article |
Structural basis of Smoothened regulation by its extracellular domains
Structural studies show that the activity of the G-protein-coupled receptor Smoothened is modulated by ligand-regulated interactions between its extracellular and transmembrane domains.
- Eamon F. X. Byrne
- , Ria Sircar
- & Christian Siebold
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Letter |
Dynamics of ribosome scanning and recycling revealed by translation complex profiling
A translation complex sequencing approach has been developed enabling intermediates of all mRNA-associated processes of translation to be isolated and localized across the transcriptome; the results support longstanding models of initiation and termination and offer new mechanistic insights.
- Stuart K. Archer
- , Nikolay E. Shirokikh
- & Thomas Preiss
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