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The melanocortin-4 receptor (MC4R) is involved in energy homeostasis and is an important drug target for syndromic obesity. We report the structure of the antagonist SHU9119-bound human MC4R at 2.8-angstrom resolution. Ca2+ is identified as a cofactor that is complexed with residues from both the receptor and peptide ligand. Extracellular Ca2+ incr...
Diabetes is a worldwide problem affecting hundreds of millions of people with increasing patient numbers every year. Our goal is to assemble a spatiotemporal, multi-scale (atomic to cellular) model of a human pancreatic β-cell to gain a more holistic understanding of β-cell function in diabetes. This effort requires the convergence of structural bi...
The construction of a predictive model of an entire eukaryotic cell that describes its dynamic structure from atomic to cellular scales is a grand challenge at the intersection of biology, chemistry, physics, and computer science. Having such a model will open new dimensions in biological research and accelerate healthcare advancements. Developing...
Signaling across cellular membranes, the 826 human G protein-coupled receptors (GPCRs) govern a wide range of vital physiological processes, making GPCRs prominent drug targets. X-ray crystallography provided GPCR molecular architectures, which also revealed the need for additional structural dynamics data to support drug development. Here, nuclear...
Assemble a spatiotemporal, multi-scale (atomic to cellular) model of a human pancreatic beta cell to gain a more holistic understanding of the beta-cell function in diabetes