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Article
Modular chimeric cytokine receptors with leucine zippers enhance the antitumour activity of CAR T cells via JAK/STAT signalling
The limited availability of cytokines in solid tumours hinders maintenance of the antitumour activity of chimeric antigen receptor (CAR) T cells. Cytokine receptor signalling pathways in CAR T cells can be act...
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Article
A genome-wide view of disordered proteins
Transcription factors containing disordered regions can now be mapped across the genome, aiding functional studies.
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Article
Open AccessDefining the condensate landscape of fusion oncoproteins
Fusion oncoproteins (FOs) arise from chromosomal translocations in ~17% of cancers and are often oncogenic drivers. Although some FOs can promote oncogenesis by undergoing liquid-liquid phase separation (LLPS)...
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Article
Open AccessDynamic spatiotemporal determinants modulate GPCR:G protein coupling selectivity and promiscuity
Recent studies have shown that G protein coupled receptors (GPCRs) show selective and promiscuous coupling to different Gα protein subfamilies and yet the mechanisms of the range of coupling preferences remain...
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Article
CCL22 mutations drive natural killer cell lymphoproliferative disease by deregulating microenvironmental crosstalk
Chronic lymphoproliferative disorder of natural killer cells (CLPD-NK) is characterized by clonal expansion of natural killer (NK) cells where the underlying genetic mechanisms are incompletely understood. In ...
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Article
Open AccessThe chemotherapeutic CX-5461 primarily targets TOP2B and exhibits selective activity in high-risk neuroblastoma
Survival in high-risk pediatric neuroblastoma has remained around 50% for the last 20 years, with immunotherapies and targeted therapies having had minimal impact. Here, we identify the small molecule CX-5461 ...
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Article
Open AccessGPCR activation mechanisms across classes and macro/microscales
Two-thirds of human hormones and one-third of clinical drugs activate ~350 G-protein-coupled receptors (GPCR) belonging to four classes: A, B1, C and F. Whereas a model of activation has been described for cla...
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Article
A community effort to bring structure to disorder
With protein structure prediction recently getting a seismic boost in accuracy, hopes are also up to better predict unstructured protein regions that can adopt diverse conformations. CAID, a community effort t...
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Article
Author Correction: Combinatorial expression of GPCR isoforms affects signalling and drug responses
An amendment to this paper has been published and can be accessed via a link at the top of the paper.
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Article
Combinatorial expression of GPCR isoforms affects signalling and drug responses
G-protein-coupled receptors (GPCRs) are membrane proteins that modulate physiology across human tissues in response to extracellular signals. GPCR-mediated signalling can differ because of changes in the sequence
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Article
Amino acid homorepeats in proteins
Amino acid homorepeats, or homorepeats, are polypeptide segments found in proteins that contain stretches of identical amino acid residues. Although abnormal homorepeat expansions are linked to pathologies suc...
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Article
Open AccessMolecular determinants underlying functional innovations of TBP and their impact on transcription initiation
TATA-box binding protein (TBP) is required for every single transcription event in archaea and eukaryotes. It binds DNA and harbors two repeats with an internal structural symmetry that show sequence asymmetry...
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Article
Open AccessA conserved molecular switch in Class F receptors regulates receptor activation and pathway selection
Class F receptors are considered valuable therapeutic targets due to their role in human disease, but structural changes accompanying receptor activation remain unexplored. Employing population and cancer geno...
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Article
Mechanisms of signalling and biased agonism in G protein-coupled receptors
G protein-coupled receptors (GPCRs) are the largest group of cell surface receptors in humans that signal in response to diverse inputs and regulate a plethora of cellular processes. Hence, they constitute one...
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Article
Molecular mechanism of modulating arrestin conformation by GPCR phosphorylation
Arrestins regulate the signaling of ligand-activated, phosphorylated G-protein-coupled receptors (GPCRs). Different patterns of receptor phosphorylation (phosphorylation barcode) can modulate arrestin conforma...
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Article
Cotranslational protein assembly imposes evolutionary constraints on homomeric proteins
Cotranslational protein folding can facilitate rapid formation of functional structures. However, it can also cause premature assembly of protein complexes, if two interacting nascent chains are in close proxi...
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Article
Visualization and analysis of non-covalent contacts using the Protein Contacts Atlas
Visualizations of biomolecular structures empower us to gain insights into biological functions, generate testable hypotheses, and communicate biological concepts. Typical visualizations (such as ball and stic...
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Article
Constraints and consequences of the emergence of amino acid repeats in eukaryotic proteins
Computational analyses of the yeast proteome and experimental work show that homorepeats facilitate protein-protein interactions and rapid protein divergence. To balance their propensity to aggregate, homorepe...
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Article
Selectivity determinants of GPCR–G-protein binding
The selective coupling of G-protein-coupled receptors (GPCRs) to specific G proteins is critical to trigger the appropriate physiological response. However, the determinants of selective binding have remained ...
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Article
Simultaneous quantification of protein order and disorder
Nuclear magnetic resonance spectroscopy is transforming our views of proteins by revealing how their structures and dynamics are closely intertwined to underlie their functions and interactions. Compelling rep...
