Ghrelin O-acyltransferase interacts with extracellular peptides and exhibits unexpected cellular localization for a secretory pathway enzyme
Campana, M. B.; Davis, T. R.; Cleverdon, E. R.; Bates, M.; Krishnan, N.; Curtis, E. R.; Childs, M. D.; Morales-Rodriguez, Y.; Sieburg, M.; Hehnly, H.; Luyt, L. G.; Hougland, J.
Show abstract
Ghrelin O-acyltransferase (GOAT) plays a central role in the maturation and activation of the peptide hormone ghrelin, which performs a wide range of endocrinological signaling roles. Using a tight-binding fluorescent ghrelin-derived peptide designed for high selectivity for GOAT over the ghrelin receptor GHS-R1a, we demonstrate that GOAT interacts with extracellular ghrelin and facilitates ligand cell internalization in both transfected cells and prostate cancer cells endogenously expressing GOAT. Coupled with enzyme mutagenesis, ligand uptake studies provide the first direct evidence supporting interaction of the putative histidine general base within GOAT with the ghrelin peptide acylation site. Our work provides a new understanding of GOATs catalytic mechanism, establishes a key step required for autocrine/paracrine ghrelin signaling involving local reacylation by GOAT, and raises the possibility that other peptide hormones may exhibit similar complexity in their intercellular and organismal-level signaling pathways.
Matching journals
The top 4 journals account for 50% of the predicted probability mass.
Similar papers in this journal
Similar papers in this journal
- Inhibition of CREB binding and function with a dual-targeting ligand 95%
- Nanomolar, noncovalent antagonism of hedgehog cholesterolysis: exception to the irreversibility rule for protein autoprocessing inhibition. 95%
- Assessing substrate scope of the cyclodehydratase LynD by mRNA display-enabled machine learning models 93%
Similar papers in this journal
- A fluorescent probe enables the discovery of improved antagonists targeting the intracellular allosteric site of the chemokine receptor CCR7 94%
- Novel bisubstrate inhibitors for protein N-terminal acetyltransferase D 94%
- Discovery of CD28-Targeted Small Molecule Inhibitors of T Cell Co-stimulation Using Affinity Selection-Mass Spectrometry (AS-MS) and Ex Vivo Validation 94%
Similar papers in this journal
- Evaluation of Alphafold modeling for elucidation of nanobody-peptide epitope interactions 94%
- Bioluminescence-based reporters for characterizing inhibitors and activators of human Sonic Hedgehog protein autoprocessing in live cells at high throughput. 94%
- Optical Control of Cell-Surface and Endomembrane-Exclusive β-Adrenergic Receptor Signaling 94%
"Similar papers" are the closest papers from that journal in the model's embedding space. They show what the match is built on, but the ranking comes mostly from a classifier over the whole training set, not from these examples alone.