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Article
Open AccessDCAF1-based PROTACs with activity against clinically validated targets overcoming intrinsic- and acquired-degrader resistance
Targeted protein degradation (TPD) mediates protein level through small molecule induced redirection of E3 ligases to ubiquitinate neo-substrates and mark them for proteasomal degradation. TPD has recently eme...
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Article
Open AccessDynamics of GLP-1R peptide agonist engagement are correlated with kinetics of G protein activation
The glucagon-like peptide-1 receptor (GLP-1R) has broad physiological roles and is a validated target for treatment of metabolic disorders. Despite recent advances in GLP-1R structure elucidation, detailed mec...
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Article
Open AccessStructure and dynamics of the active Gs-coupled human secretin receptor
The class B secretin GPCR (SecR) has broad physiological effects, with target potential for treatment of metabolic and cardiovascular disease. Molecular understanding of SecR binding and activation is importan...
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Article
Cryo-EM structure of the active, Gs-protein complexed, human CGRP receptor
Calcitonin gene-related peptide (CGRP) is a widely expressed neuropeptide that has a major role in sensory neurotransmission. The CGRP receptor is a heterodimer of the calcitonin receptor-like receptor (CLR) c...
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Article
Structure of the adenosine-bound human adenosine A1 receptor–Gi complex
The class A adenosine A1 receptor (A1R) is a G-protein-coupled receptor that preferentially couples to inhibitory Gi/o heterotrimeric G proteins, has been implicated in numerous diseases, yet remains poorly targe...
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Article
Phase-plate cryo-EM structure of a biased agonist-bound human GLP-1 receptor–Gs complex
The structure of the glucagon-like peptide 1 receptor (GLP-1R) with its biased agonist exendin-P5 sheds light on both receptor activation and the mechanism of biased agonism.
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Article
Open AccessCryo-EM structure of haemoglobin at 3.2 Å determined with the Volta phase plate
With the advent of direct electron detectors, the perspectives of cryo-electron microscopy (cryo-EM) have changed in a profound way. These cameras are superior to previous detectors in co** with the intrinsi...
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Article
Phase-plate cryo-EM structure of a class B GPCR–G-protein complex
Class B G-protein-coupled receptors are major targets for the treatment of chronic diseases, such as osteoporosis, diabetes and obesity. Here we report the structure of a full-length class B receptor, the calc...
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Article
Open AccessVolta phase plate cryo-EM of the small protein complex Prx3
Cryo-EM of large, macromolecular assemblies has seen a significant increase in the numbers of high-resolution structures since the arrival of direct electron detectors. However, sub-nanometre resolution cryo-E...
