Article
|
Open Access
Featured
-
-
Article
| Open AccessPolymorphic amyloid nanostructures of hormone peptides involved in glucose homeostasis display reversible amyloid formation
In this work, the authors highlight that conserved receptor binding segments of class B GPCR ligands have a dual nature: they serve as amyloid-prone regions involved in pH-dependent conversion from secretory amyloid fibrils to the functional folded form.
- Dániel Horváth
- , Zsolt Dürvanger
- & András Perczel
-
Article
| Open AccessStructural basis for the activation and ligand recognition of the human oxytocin receptor
Here, Waltenspühl et al. report the cryo-EM structure of active human oxytocin receptor in complex with oxytocin and with a heterotrimeric G protein, providing insights into this hormone system critically involved in the regulation of social behaviour and reproduction.
- Yann Waltenspühl
- , Janosch Ehrenmann
- & Andreas Plückthun
-
Article
| Open AccessMolecular recognition of an acyl-peptide hormone and activation of ghrelin receptor
Ghrelin is a gastric peptide hormone and its acylation is required for binding to and activation of the ghrelin receptor in the brain, which initiates appetite. Here, the authors present cryo-EM structures of the Gq-coupled ghrelin receptor bound to ghrelin and the synthetic agonist GHRP-6 and they describe how the acylated peptide hormone is recognised by the receptor, which is of interest for drug design.
- Yue Wang
- , Shimeng Guo
- & Yi Jiang
-
Article
| Open AccessStructural basis for ligand recognition of the neuropeptide Y Y2 receptor
The human neuropeptide Y receptor Y2 (Y2R) is a drug target for the treatment of obesity and anxiety. Crystal structure of Y2R bound to a selective antagonist and accompanying mutagenesis provide insights into ligand recognition and subtype specificity of NPY receptors.
- Tingting Tang
- , Christin Hartig
- & Beili Wu
-
Article
| Open AccessAn atlas of O-linked glycosylation on peptide hormones reveals diverse biological roles
O-glycosylation is an abundant post-translational modification but its relevance for bioactive peptides is unclear. Here, the authors detect O-glycans on almost one third of the classified peptide hormones and show that O-glycosylation can modulate peptide half-lives and receptor activation properties.
- Thomas D. Madsen
- , Lasse H. Hansen
- & Katrine T. Schjoldager
-
Article
| Open AccessStructure of an antagonist-bound ghrelin receptor reveals possible ghrelin recognition mode
Ghrelin is a gastric peptide hormone with important physiological functions, including growth hormone release and appetite-stimulating activity. Here, authors solved the crystal structure of the ghrelin receptor bound to antagonist and suggested a possible mechanism of activation by acyl-modified ghrelin.
- Yuki Shiimura
- , Shoichiro Horita
- & Masayasu Kojima
-
Article
| Open AccessFemtosecond X-ray coherent diffraction of aligned amyloid fibrils on low background graphene
The structures of amyloid fibres are currently primarily studied through solid state NMR and cryo-EM. Here the authors present a free-standing graphene support device that allows diffraction imaging of non-crystalline amyloid fibrils with single X-ray pulses from an X-ray free-electron laser.
- Carolin Seuring
- , Kartik Ayyer
- & Henry N. Chapman
-
Article
| Open AccessAwake dynamics and brain-wide direct inputs of hypothalamic MCH and orexin networks
Hypothalamic neurons expressing melanin-concentrating-hormone (MCH) maintain body weight by orchestrating behaviour and metabolism, but little is known about their intrinsic regulation. Here, Gonzalez and colleagues reveal their behaviour-related dynamics during wakefulness, and map their brain-wide neural inputs.
- J. Antonio González
- , Panagiota Iordanidou
- & Denis Burdakov
-
Article
| Open AccessThe complex binding mode of the peptide hormone H2 relaxin to its receptor RXFP1
The mechanism by which relaxin activates the relaxin family peptide receptor-1 is poorly understood. Here, Sethi et al.identify a relaxin binding site in an extracellular linker between the LDLa and LRR domains and propose that relaxin binding stabilizes a helical conformation that leads to receptor activation.
- Ashish Sethi
- , Shoni Bruell
- & Paul R. Gooley
-
Article
| Open AccessmTORC1 regulates PTHrP to coordinate chondrocyte growth, proliferation and differentiation
mTORC1 is crucial for chondrocyte proliferation and bone growth, but the downstream signalling is not clear. Here, the authors use rapamycin and chondrocyte-specific Tsc1 knockout mice to show that S6K1 can cause nuclear accumulation of Gli2, thus driving PTHrP expression and preventing terminal differentiation of prehypertrophic chondrocytes.
- Bo Yan
- , Zhongmin Zhang
- & Xiaochun Bai
-
Article
| Open AccessGenome-wide meta-analysis uncovers novel loci influencing circulating leptin levels
This meta-analysis of genome-wide association studies identifies four genetic loci associated with circulating leptin levels independent of adiposity. Examination in mouse adipose tissue explants provides functional support for the leptin-associated loci.
- Tuomas O. Kilpeläinen
- , Jayne F. Martin Carli
- & Ruth J. F. Loos
-
Article |
Identification and optimization of small-molecule agonists of the human relaxin hormone receptor RXFP1
The peptide hormone relaxin has potential in the treatment of acute heart failure, but it must be intravenously injected and has a short half-life after administration. Now, small-molecule alternatives to relaxin are reported with similar efficacies to the natural hormone in functional assays.
- Jingbo Xiao
- , Zaohua Huang
- & Juan J. Marugan