Cargando…

Cellular Uptake of a Fluorescent Ligand Reveals Ghrelin O-Acyltransferase Interacts with Extracellular Peptides and Exhibits Unexpected Localization for a Secretory Pathway Enzyme

[Image: see text] 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 o...

Descripción completa

Detalles Bibliográficos
Autores principales: Campaña, Maria B., Davis, Tasha R., Novak, Sadie X., Cleverdon, Elizabeth R., Bates, Michael, Krishnan, Nikhila, Curtis, Erin R., Childs, Marina D., Pierce, Mariah R., Morales-Rodriguez, Yasandra, Sieburg, Michelle A., Hehnly, Heidi, Luyt, Leonard G., Hougland, James L.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Chemical Society 2023
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10442857/
https://www.ncbi.nlm.nih.gov/pubmed/37494676
http://dx.doi.org/10.1021/acschembio.3c00334
Descripción
Sumario:[Image: see text] 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 GHSR, 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 support the interaction of the putative histidine general base within GOAT with the ghrelin peptide acylation site. Our work provides a new understanding of GOAT’s catalytic mechanism, establishes that GOAT can interact with ghrelin and other peptides located outside the cell, and raises the possibility that other peptide hormones may exhibit similar complexity in their intercellular and organismal-level signaling pathways.