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Assembly of Weibel–Palade body-like tubules from N-terminal domains of von Willebrand factor
- Source :
- Proceedings of the National Academy of Sciences. 105:482-487
- Publication Year :
- 2008
- Publisher :
- Proceedings of the National Academy of Sciences, 2008.
-
Abstract
- Endothelial cells assemble von Willebrand factor (VWF) multimers into ordered tubules within storage organelles called Weibel–Palade bodies, and tubular packing is necessary for the secretion of VWF filaments that can bind connective tissue and recruit platelets to sites of vascular injury. We now have recreated VWF tubule assembly in vitro , starting with only pure VWF propeptide (domains D1D2) and disulfide-linked dimers of adjacent N-terminal D′D3 domains. Assembly requires low pH and calcium ions and is reversed at neutral pH. Quick-freeze deep-etch electron microscopy and three-dimensional reconstruction of negatively stained images show that tubules contain a repeating unit of one D′D3 dimer and two propeptides arranged in a right-handed helix with 4.2 units per turn. The symmetry and location of interdomain contacts suggest that decreasing pH along the secretory pathway coordinates the disulfide-linked assembly of VWF multimers with their tubular packaging.
- Subjects :
- Light
Protein Conformation
Imaging, Three-Dimensional
Protein structure
Von Willebrand factor
von Willebrand Factor
Organelle
Image Processing, Computer-Assisted
Weibel–Palade body
Humans
Scattering, Radiation
Platelet
Disulfides
Protein precursor
Secretory pathway
Ions
Multidisciplinary
Weibel-Palade Bodies
biology
Chemistry
Lasers
Hydrogen-Ion Concentration
Biological Sciences
Protein Structure, Tertiary
Microscopy, Electron
Tubule
Biochemistry
Biophysics
biology.protein
Peptides
Dimerization
Subjects
Details
- ISSN :
- 10916490 and 00278424
- Volume :
- 105
- Database :
- OpenAIRE
- Journal :
- Proceedings of the National Academy of Sciences
- Accession number :
- edsair.doi.dedup.....cd278051a777f50ccfd7d88480d5d1f0