Skip to main content

Data for: Inhibition of Ca2+-triggered secretion by hydrocarbon-stapled peptides

Cite this dataset

Brunger, Axel et al. (2022). Data for: Inhibition of Ca2+-triggered secretion by hydrocarbon-stapled peptides [Dataset]. Dryad.


Ca2+-triggered membrane fusion is orchestrated by a conserved set of proteins to mediate synaptic neurotransmitter release, mucin secretion, and other regulated exocytic processes. For neurotransmitter release, the Ca2+ sensitivity is introduced by interactions between the Ca2+ sensor synaptotagmin and the SNARE complex, and sequence conservation and functional studies suggest this mechanism is also conserved for mucin secretion. Disruption of Ca2+-triggered membrane fusion by a pharmacologic agent would have therapeutic value for mucus hypersecretion since it is the major cause of airway obstruction in the pathophysiology of respiratory viral infection, asthma, COPD and cystic fibrosis. We designed a hydrocarbon-stapled peptide that specifically disrupts Ca2+-triggered membrane fusion by interfering with the so-called primary interface between the neuronal SNARE complex and Ca2+ binding C2B domain of synaptotagmin-1. In reconstituted systems with these neuronal synaptic proteins or with their airway homologues syntaxin-3, SNAP-23, VAMP8, synaptotagmin-2, along with Munc13-2 and Munc18-2, the stapled peptide strongly suppressed Ca2+-triggered fusion at physiological Ca2+ concentrations. Conjugation of cell penetrating peptides to the stapled peptide resulted in efficient delivery into cultured human airway epithelial cells and mouse airway epithelium, where it markedly and specifically reduced stimulated mucin secretion in both systems, and substantially attenuated mucus occlusion of mouse airways. Taken together, peptides that disrupt Ca2+-triggered membrane fusion may allow therapeutic modulation of mucin secretory pathways. This data set contains the imaging data for the studies of primary human airway epithelial cells (HAECs), for the mucin secretion and airway mucus occlusion studies in mice, and the NAMD input files and trajectories of the molecular dynamics simulations.

Usage notes

There are individual README files in each of the directories. 


National Cancer Institute, Award: R01MH63105

National Heart Lung and Blood Institute, Award: R01HL129795

National Institute of Allergy and Infectious Diseases, Award: R21AI137319

Deutsche Forschungsgemeinschaft, Award: 251293561

Deutsche Forschungsgemeinschaft, Award: 175083951

Cystic Fibrosis Foundation, Award: DICKEY18G0

Cystic Fibrosis Foundation, Award: DICKEY19P0