Article
|
Open Access
Featured
-
-
Article
| Open AccessStructure and mechanism of the alkane-oxidizing enzyme AlkB
Alkane monooxygenase (AlkB) plays a key role in the global carbon cycle and remediation of oil spills. Here, the authors report the cryo-EM structure of AlkB to provide insight into the catalytic mechanism and substrate selectivity.
- Xue Guo
- , Jianxiu Zhang
- & Liang Feng
-
Article
| Open AccessControlling protein stability with SULI, a highly sensitive tag for stabilization upon light induction
Tools for the spatiotemporal control of protein abundance are valuable in studying diverse complex biological processes. Here, authors engineered a protein tag which is stabilized upon light induction but which quickly degrades the protein of interest in the dark, demonstrating control of protein stability in yeast and zebrafish.
- Miaowei Mao
- , Yajie Qian
- & Yi Yang
-
Article
| Open AccessSynDLP is a dynamin-like protein of Synechocystis sp. PCC 6803 with eukaryotic features
In eukaryotes, dynamins and dynamin-like proteins (DLPs) are involved in various membrane remodeling processes. Here, the authors present the structure and functional characterization of a DLP of the cyanobacterium Synechocystis sp. PCC 6803.
- Lucas Gewehr
- , Benedikt Junglas
- & Dirk Schneider
-
Article
| Open AccessConstrained catecholamines gain β2AR selectivity through allosteric effects on pocket dynamics
Constrained catecholamines gain β2AR selectivity. Although the orthosteric pockets are identical in β1AR and β2AR, surrounding residues allosterically modify the pockets and contribute to the β2AR selectivity of the constrained catecholamines.
- Xinyu Xu
- , Jeremy Shonberg
- & Peter Gmeiner
-
Comment
| Open AccessStructural insights into how augmin augments the mitotic spindle
Cell division critically requires amplification of microtubules (MTs) in the bipolar mitotic spindle. This relies on the filamentous augmin complex that enables MT branching. Studies by Gabel et al., Zupa et al. and Travis et al. describe consistent integrated atomic models of the extraordinarily flexible augmin complex. Their work prompts the question: what is this flexibility really needed for?
- Szymon W. Manka
-
Article
| Open AccessIntegrated model of the vertebrate augmin complex
Many microtubules in the mitotic spindle are made through microtubule branching. Here, the authors report a structural model of the augmin complex and insights into its role in microtubule branching.
- Sophie M. Travis
- , Brian P. Mahon
- & Sabine Petry
-
Article
| Open AccessThe RNA-binding protein landscapes differ between mammalian organs and cultured cells
Characterization of RNA-binding proteins (RBPs) in tissues has been hampered by technical constraints. Here, the authors describe ex vivo eRIC, a method for global profiling of RBPs active in mammalian organs, and report comprehensive RBP atlases from mouse brain, kidney and liver.
- Joel I. Perez-Perri
- , Dunja Ferring-Appel
- & Matthias W. Hentze
-
Article
| Open AccessCryo-EM structures of mitochondrial ABC transporter ABCB10 in apo and biliverdin-bound form
ABCB10 is a mitochondrial biliverdin exporter. Here, authors report the cryo-EM structures of ABCB10 apo and biliverdin-bound forms, revealing a cholesterol binding site that promotes the ATPase activity and thermostability of ABCB10.
- Sheng Cao
- , Yihu Yang
- & Zhuqing Ouyang
-
Article
| Open AccessA cationic motif upstream Engrailed2 homeodomain controls cell internalization through selective interaction with heparan sulfates
Here, the authors show that cell internalization of Engrailed2 not only relies on its homeodomain, but also involves a cationic region which interacts selectively with cell surface heparan sulfates.
- Sébastien Cardon
- , Yadira P. Hervis
- & Sandrine Sagan
-
Article
| Open AccessConformational cycle of human polyamine transporter ATP13A2
ATP13A2 is a lysosomal polyamine transporter, mutated in several diseases including juvenile-onset Parkinson’s disease. Here, the authors report structures of human ATP13A2 in six distinct intermediate states, illustrating most of its conformational cycle.
- Jianqiang Mu
- , Chenyang Xue
- & Zhongmin Liu
-
Article
| Open AccessTargeting USP2 regulation of VPRBP-mediated degradation of p53 and PD-L1 for cancer therapy
The clinical success of restoring P53 for cancer therapy has been limited due to toxicity. Here, the authors identify USP2 as an upstream regulator of VPRBP-mediated degradation of p53 and PD-L1 and demonstrate the efficacy of combining USP2 inhibitor and PD-L1/PD-1 immune checkpoint blockade in cancers.
- Jingjie Yi
- , Omid Tavana
- & Wei Gu
-
Article
| Open AccessStructure of the heterotrimeric membrane protein complex FtsB-FtsL-FtsQ of the bacterial divisome
The FtsB-FtsL-FtsQ complex is essential for regulating cell wall synthesis during bacterial cell division. Here, authors report the full-length trimeric structure showing a tilted V-shaped conformation and suggest an allosteric regulatory mechanism.
- Hong Thuy Vy Nguyen
- , Xiaorui Chen
- & Che Ma
-
Article
| Open AccessSingle-molecule fingerprinting of protein-drug interaction using a funneled biological nanopore
Efficient screening of protein-drug interactions (PDIs) has been impeded by the limitations of current biophysical approaches. Here, the authors present a funneled YaxAB nanopore sensor which allows label-free, single-molecule detection of proteins and PDIs.
- Ki-Baek Jeong
- , Minju Ryu
- & Seung-Wook Chi
-
Article
| Open AccessStructure and mechanism of oxalate transporter OxlT in an oxalate-degrading bacterium in the gut microbiota
In our gut, oxalate-degrading bacteria absorb oxalate, a causative substance for kidney stone formation, and reduce our health risk. In this work, the authors report the structure of the oxalate transporter responsible for this process and how the protein works.
- Titouan Jaunet-Lahary
- , Tatsuro Shimamura
- & Atsuko Yamashita
-
Article
| Open AccessThe structural basis of the pH-homeostasis mediated by the Cl−/HCO3− exchanger, AE2
Cells maintain a narrow physiological pH by exchanging intracellular bicarbonate for extracellular chloride. Here, authors determine the cryo-EM structures of human anion exchanger 2 (AE2) in five major operating states and one transitional state, to collectively demonstrate the process of pH-balancing.
- Qing Zhang
- , Liyan Jian
- & Yu Cao
-
Article
| Open AccessMutation in glutamate transporter homologue GltTk provides insights into pathologic mechanism of episodic ataxia 6
Episodic ataxias (EAs) are rare neurological conditions that cause motor impairment. Here the authors investigated the molecular mechanism of such a pathological condition caused by a mutation of a conserved proline into arginine residue.
- Emanuela Colucci
- , Zaid R. Anshari
- & Albert Guskov
-
Article
| Open AccessA Vaccinia-based system for directed evolution of GPCRs in mammalian cells
G protein-coupled receptors are a major class of drug targets. Here, the authors develop a method whereby their biophysical and functional properties can be altered through directed evolution in mammalian cells, leading to variants exhibiting features such as high stability and expression, or increased allosteric coupling.
- Christoph Klenk
- , Maria Scrivens
- & Andreas Plückthun
-
Article
| Open AccessStructural insights into the human niacin receptor HCA2-Gi signalling complex
Hydroxyl-carboxylic acid receptor 2 (HCA2) functions as a high-affinity receptor for nicotinic acid (vitamin B3). Here, authors report the cryo-EM structure of the HCA2-Gi complex with the agonist MK-6892 and inactive state crystal structures of mutation stabilized HCA2, to describe the mechanism of HCA2 signaling.
- Yang Yang
- , Hye Jin Kang
- & Zhi-Jie Liu
-
Article
| Open AccessNeutron-encoded diubiquitins to profile linkage selectivity of deubiquitinating enzymes
Most insights into deubiquitinase (DUB) substrate specificity originate from studies with isolated di-ubiquitins (diUb), but in cells diUbs with different linkage types coexist. Here, the authors develop a mass spectrometric DUB activity assay that can probe all diUbs simultaneously under substrate competition conditions.
- Bianca D. M. van Tol
- , Bjorn R. van Doodewaerd
- & Paul P. Geurink
-
Article
| Open AccessTemporal and spatial assembly of inner ear hair cell ankle link condensate through phase separation
In this work, the authors demonstrate that LLPS of the quaternary USH2 protein complex initiates the formation of stereociliary ankle link condensates, providing insights into the pathogenesis of deafness.
- Huang Wang
- , Haibo Du
- & Qing Lu
-
Article
| Open AccessSmall molecule-nanobody conjugate induced proximity controls intracellular processes and modulates endogenous unligandable targets
Induced proximity can be used to control diverse cellular processes. Here, the authors develop nanobody-based proximity inducers called SNACIPs, which can be used to regulate either tagged or endogenous proteins, and demonstrate their use in blocking microtubule nucleation for tumour growth inhibition in vivo.
- Xiaofeng Sun
- , Chengjian Zhou
- & Xi Chen
-
Article
| Open AccessA generalizable nanopore sensor for highly specific protein detection at single-molecule precision
Sensitive and accurate approaches for protein detection have many potential applications. Here the authors show how engineered protein nanopore sensors, consisting of a monobody fused to a single-polypeptide nanopore, can be used for highly specific detection of proteins in complex biofluids.
- Mohammad Ahmad
- , Jeung-Hoi Ha
- & Liviu Movileanu
-
Article
| Open AccessThe structural flexibility of MAD1 facilitates the assembly of the Mitotic Checkpoint Complex
The formation of the mitotic checkpoint complex requires an intricate spatial coordination amongst the proteins Bub1, Mad1, Cdc20, and Mad2. Chen et al show that a structural flexibility in Mad1 plays an essential role in achieving this coordination.
- Chu Chen
- , Valentina Piano
- & Ajit P. Joglekar
-
Article
| Open AccessThe architecture of transmembrane and cytoplasmic juxtamembrane regions of Toll-like receptors
Toll-like receptors (TLRs) play a key role in the innate immune system. Here, Kornilov et al. resolve the 3D structures of the membrane-associated parts of four TLRs to reveal properties of the juxta-membrane domain.
- F. D. Kornilov
- , A. V. Shabalkina
- & K. S. Mineev
-
Article
| Open AccessStructural basis of vitamin C recognition and transport by mammalian SVCT1 transporter
Sodium-dependent vitamin C transporters are responsible for vitamin C uptake and tissue distribution in mammals. Here, authors present cryo-EM structures of mouse SVCT1 in both the apo and substrate-bound states, revealing the structural basis of substrate recognition and transport.
- Mingxing Wang
- , Jin He
- & Ji She
-
Article
| Open AccessCryo-EM structures of human Cx36/GJD2 neuronal gap junction channel
Connexin 36 (Cx36) gap junction channel is responsible for signal transmission in electrical synapses. Here, the authors determine cryo-EM structures of Cx36, providing insights into a potential role of lipids in the channel gating.
- Seu-Na Lee
- , Hwa-Jin Cho
- & Hyung Ho Lee
-
Article
| Open AccessMolecular mechanism of biased signaling at the kappa opioid receptor
Biased signaling in κ-opiod receptors (KOR) offer an attractive strategy for pain management. Here the authors identify determinants of KOR signaling bias using structural methods in combination with molecular dynamics simulations.
- Amal El Daibani
- , Joseph M. Paggi
- & Tao Che
-
Article
| Open AccessIntermediate-state-trapped mutants pinpoint G protein-coupled receptor conformational allostery
Understanding of GPCR activation is limited as the structural information fails to present the full spectrum of energy landscape. Here, authors establish a series of conformation-biased mutants that represent five conformational states lying along adenosine A2A receptor (A2AR) activation.
- Xudong Wang
- , Chris Neale
- & Libin Ye
-
Article
| Open AccessTwo-step structural changes in M3 muscarinic receptor activation rely on the coupled Gq protein cycle
During Gq protein activation, the separated Gαq-GTP forms a stable complex with the ligand-activated hM3R and PLCβ. Here the authors demonstrate that a single M3 receptor FRET probe can display the real-time conformational dynamics of innate receptor by the downstream Gq protein cycle.
- Yong-Seok Kim
- , Jun-Hee Yeon
- & Byung-Chang Suh
-
Article
| Open AccessStructural basis of peptide recognition and activation of endothelin receptors
Endothelin receptors (ETAR and ETBR) are critical for vasoregulation and are targets for cardiovascular diseases treatment. Here, the authors offer a structural basis for peptide recognition selectivity and activation of both endothelin receptors.
- Yujie Ji
- , Jia Duan
- & Yi Jiang
-
Article
| Open AccessStructural basis of HIV-1 maturation inhibitor binding and activity
HIV maturation inhibitors such as bevirimat (BVM) interfering with Gag processing are emerging as alternative anti-retroviral drug candidates. Here, the authors report structures of assemblies of HIV-1 Gag fragments spanning the CA C-terminal domain and SP1 region bound to BVM.
- Sucharita Sarkar
- , Kaneil K. Zadrozny
- & Tatyana Polenova
-
Article
| Open AccessThe dynamic nature of netrin-1 and the structural basis for glycosaminoglycan fragment-induced filament formation
In this work, the authors report that heparin oligosaccharides have a significant impact on the highly dynamic behaviour of netrin-1 by inducing hierarchical and distinct super assemblies leading to unique, yet unknown netrin-1 filament formation.
- Markus Meier
- , Monika Gupta
- & Jörg Stetefeld
-
Article
| Open AccessLigand-specific changes in conformational flexibility mediate long-range allostery in the lac repressor
Using hydrogen-deuterium exchange, the authors propose a model explaining how a classic transcription factor undergoes changes in its conformational ensemble in response to different ligands.
- Anum Glasgow
- , Helen T. Hobbs
- & Tanja Kortemme
-
Article
| Open AccessrRNA methylation by Spb1 regulates the GTPase activity of Nog2 during 60S ribosomal subunit assembly
Regulation of 60S biogenesis remains poorly understood. Using cryo-EM, the authors show that failure of Spb1 to methylate the A-loop nucleotide G2922 prematurely activates the GTPase Nog2, suggesting that Spb1 and Nog2 form a kinetic checkpoint during ribosome maturation.
- Kamil Sekulski
- , Victor Emmanuel Cruz
- & Jan P. Erzberger
-
Article
| Open AccessStructural details of a Class B GPCR-arrestin complex revealed by genetically encoded crosslinkers in living cells
The conformation of GPCR-arrestin complexes at the cell membrane, despite available structures, remains uncertain. This work reveals structure and dynamics of the PTH1R-arrestin2 complex, including flexible regions, in live cells.
- Yasmin Aydin
- , Thore Böttke
- & Irene Coin
-
Article
| Open AccessCell surface protein aggregation triggers endocytosis to maintain plasma membrane proteostasis
How cells respond to denaturation of extracellular protein domains remained largely unknown. Here, authors describe an aggregation-dependent endocytosis pathway, facilitating uptake and degradation of antibody- and stress-induced protein aggregates.
- David Paul
- , Omer Stern
- & Harvey McMahon
-
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
-
Article
| Open AccessThe translating bacterial ribosome at 1.55 Å resolution generated by cryo-EM imaging services
Developments in cryo-EM sample preparation and data collection are pivotal for structure determination. Fromm et al. present a 1.55 Å structure of the translating bacterial ribosome that provides new insights on its function and may allow for more precise structure-based drug design.
- Simon A. Fromm
- , Kate M. O’Connor
- & Simone Mattei
-
Article
| Open AccessThe cofactor-dependent folding mechanism of Drosophila cryptochrome revealed by single-molecule pulling experiments
Characterizing folding pathways of large proteins that bind complex cofactors is challenging. The authors use optical tweezers to study the 542-residue FAD-binding lightsensor protein dCRY, identifying several intermediates and cofactor binding steps, and dissecting the role of FAD moieties in folding.
- Sahar Foroutannejad
- , Lydia L. Good
- & Rodrigo A. Maillard
-
Article
| Open AccessStructural basis of lysophosphatidylserine receptor GPR174 ligand recognition and activation
GPR174 is a lysophosphatidylserine (LysoPS) activated GPCR. Here, the authors report the cryo-EM structure of LysoPS-bound human GPR174 in complex with Gs protein. The study reveals how GPR174 recognizes the lipid ligand and engages Gs in a distinct binding mode.
- Jiale Liang
- , Asuka Inoue
- & Yuanzheng He
-
Article
| Open AccessProspect of acromegaly therapy: molecular mechanism of clinical drugs octreotide and paltusotine
Somatostatin receptor 2 (SSTR2) represents a therapeutic target of neuroendocrine tumors. Here, authors report two structures of SSTR2 bound to peptide octreotide and small molecule paltusotine, revealing the basis subtype selectivity and signal bias properties.
- Jie Zhao
- , Hong Fu
- & Zhenhua Shao
-
Article
| Open AccessIdentification of global inhibitors of cellular glycosylation
Here, the authors discover small molecules that inhibit glycosylation processes that occur in the Golgi apparatus of cells. The molecules reversibly inhibit formation of elaborate glycan structures without affecting secretion of glycoproteins.
- Daniel Madriz Sørensen
- , Christian Büll
- & Yoshiki Narimatsu
-
Article
| Open AccessThe ϕPA3 phage nucleus is enclosed by a self-assembling 2D crystalline lattice
To protect from host attack, numerous jumbo bacteriophages establish a micron-scale, protein-based structure to enclose their replicating DNA. Using cryoEM, the authors show that the 2D crystal enclosing this so-called phage nucleus is an assembly of tetramers linked by flexible loops and tails.
- Eliza S. Nieweglowska
- , Axel F. Brilot
- & David A. Agard
-
Article
| Open AccessConformational changes in the human Cx43/GJA1 gap junction channel visualized using cryo-EM
Gap junction intercellular channels (GJIChs) facilitate direct communication between adjacent cells. Here, authors provide high-resolution information on dynamic structural changes in Cx43 GJICh that are necessary to understand the gating mechanism.
- Hyuk-Joon Lee
- , Hyung Jin Cha
- & Jae-Sung Woo
-
Article
| Open AccessNative structure of mosquito salivary protein uncovers domains relevant to pathogen transmission
Female mosquitoes inject saliva into vertebrate hosts during blood feeding, transmitting mosquito-borne pathogens. Here, cryo-EM of mosquito salivary gland extract uncovers the native SGS1 structure and domains relevant to pathogen transmission.
- Shiheng Liu
- , Xian Xia
- & Z. Hong Zhou
-
Article
| Open AccessWatching the release of a photopharmacological drug from tubulin using time-resolved serial crystallography
Photopharmacology manipulates the biological activity of small molecules by light. Using an X-ray laser, the authors follow the release of the drug azo-combretastatin A4 from tubulin and the concomitant structural changes over nine orders of magnitude in time.
- Maximilian Wranik
- , Tobias Weinert
- & Jörg Standfuss
-
Article
| Open AccessStructural basis for membrane attack complex inhibition by CD59
CD59 protects human cells from damage by the MAC immune pore. The authors show how CD59 inhibits MAC, by deflecting pore-forming β-hairpins of complement proteins. As well as how the membrane environment influences the role of CD59 in complement regulation and in host-pathogen interactions.
- Emma C. Couves
- , Scott Gardner
- & Doryen Bubeck
-
Article
| Open AccessStructure of the planar cell polarity cadherins Fat4 and Dachsous1
Fat and Dachsous are large cadherins that regulate planar polarity as a receptor:ligand pair. Here, authors determine the structure of the Fat:Dachsous complex to uncover the molecular determinants of binding and posttranslational modification.
- Elliot Medina
- , Yathreb Easa
- & Vincent C. Luca
-
Article
| Open AccessRhodobacter capsulatus forms a compact crescent-shaped LH1–RC photocomplex
Rhodobacter capsulatus is a favored model organism for studying bacterial photosynthesis. Here the authors present a structure of its light-harvesting–reaction center complex, which reveals that it forms a crescent shape containing only 10 LH1 αβ-subunits.
- Kazutoshi Tani
- , Ryo Kanno
- & Zheng-Yu Wang-Otomo
Browse broader subjects
Browse narrower subjects
- Acetyltransferases
- Blood proteins
- Carrier proteins
- Cell-cycle proteins
- Cerebrospinal fluid proteins
- Chaperones
- Chromatin
- Circadian rhythm signalling peptides and proteins
- Colipases
- Complement
- Contractile proteins
- Cytoskeletal proteins
- DNA-binding proteins
- G protein-coupled receptors
- Glycoproteins
- GTP-binding protein regulators
- Integrins
- Intracellular signalling peptides and proteins
- Lectins
- Lipoproteins
- Membrane proteins
- Metalloproteins
- Methylases
- Mitochondrial proteins
- Nuclear receptors
- Nucleases
- Nucleoproteins
- Nucleotide-binding proteins
- Oncogene proteins
- Phosphoproteins
- Phosphorylases
- Proteome
- Ribosomal proteins
- RNA-binding proteins
- Scleroproteins
- Selenium-binding proteins
- Sumoylated proteins
- Thioredoxins
- Transcription factors
- Tumour-suppressor proteins
- Ubiquitins
- Ubiquitylated proteins
- Viral proteins