ArticleProceedings of the National Academy of Sciences of the United States of America2009
Functional and structural characterization of a dense core secretory granule sorting domain from the PC1/3 protease.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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Who cites it
18 citing papers in PubMed.
- Cell-specific secretory granule sorting mechanisms: the role of MAGEL2 and retromer in hypothalamic regulated secretion.Frontiers in cell and developmental biology · 2023Review
- Small disulfide loops in peptide hormones mediate self-aggregation and secretory granule sorting.Life science alliance · 2022Article
- Molecular evolution of PCSK family: Analysis of natural selection rate and gene loss.PloS one · 2021Article
- Pathways of Glucagon Secretion and Trafficking in the Pancreatic Alpha Cell: Novel Pathways, Proteins, and Targets for Hyperglucagonemia.Frontiers in endocrinology · 2021Review
- SERCA2 Deficiency Impairs Pancreatic β-Cell Function in Response to Diet-Induced Obesity.Diabetes · 2016Article
- The EARP Complex and Its Interactor EIPR-1 Are Required for Cargo Sorting to Dense-Core Vesicles.PLoS genetics · 2016Article
- PCSK1 Variants and Human Obesity.Progress in molecular biology and translational science · 2016Review
- Revisiting PC1/3 Mutants: Dominant-Negative Effect of Endoplasmic Reticulum-Retained Mutants.Endocrinology · 2015Article
- Biochemical and cell biological properties of the human prohormone convertase 1/3 Ser357Gly mutation: a PC1/3 hypermorph.Endocrinology · 2014Article
- Two dipolar α-helices within hormone-encoding regions of proglucagon are sorting signals to the regulated secretory pathway.The Journal of biological chemistry · 2014Article
- Article
- Role of adaptor proteins in secretory granule biogenesis and maturation.Frontiers in endocrinology · 2013Article
- Disruption of proprotein convertase 1/3 (PC1/3) expression in mice causes innate immune defects and uncontrolled cytokine secretion.The Journal of biological chemistry · 2012Article
- Exploring the membrane topology of prohormone convertase 1 in AtT20 Cells: in situ analysis by immunofluorescence microscopy.F1000Research · 2012Article
- Parotid secretory protein binds phosphatidylinositol (3,4) bisphosphate.Journal of dental research · 2011Article
- Forward targeting of Toxoplasma gondii proproteins to the micronemes involves conserved aliphatic amino acids.Traffic (Copenhagen, Denmark) · 2011Article
- Chromogranin A as a crucial factor in the sorting of peptide hormones to secretory granules.Cellular and molecular neurobiology · 2010Review
- Modulation of prohormone convertase 1/3 properties using site-directed mutagenesis.Endocrinology · 2010Article
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Authors and funding
7 authors.
Funding
Abstract
Several peptide hormones are initially synthesized as inactive precursors. It is only on entry of these prohormones and their processing proteases into dense core secretory granules (DCSGs) that the precursors are cleaved to generate their active forms. Prohormone convertase (PC)1/3 is a processing protease that is targeted to DCSGs. The signal for targeting PC1/3 to DCSGs resides in its carboxy-terminal tail (PC1/3(617-753)), where 3 regions (PC1/3(617-625), PC1/3(665-682), and PC1/3(711-753)) are known to aid in sorting and membrane association. In this article, we have determined a high-resolution structure of the extreme carboxy-terminal sorting domain, PC1/3(711-753) in micelles by NMR spectroscopy. PC1/3(711-753) contains 2 alpha helices located between residues 722-728 and 738-750. Functional assays demonstrate that the second helix (PC1/3(738-750)) is necessary and sufficient to target a constitutively secreted protein to granules, and that L(745) anchors a hydrophobic patch that is critical for sorting. Also, we demonstrate that calcium binding by the second helix of PC1/3(711-753) promotes aggregation of the domain via the hydrophobic patch centered on L(745). These results provide a structure-function analysis of a DCSG-sorting domain, and reveal the importance of a hydrophobic patch and calcium binding in controlling the sorting of proteins containing alpha helices to DCSGs.
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