Assembly of Weibel-Palade body-like tubules from N-terminal domains of von Willebrand factor

Proceedings of the National Academy of Sciences of the United States of America
Ren-Huai HuangJ Evan Sadler

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.

References

Nov 1, 1989·Journal of Electron Microscopy Technique·J Heuser
Oct 1, 1985·The Journal of Clinical Investigation·W E FowlerP A McKee
Sep 5, 1983·Journal of Molecular Biology·J E Heuser
Oct 6, 1998·Annual Review of Biochemistry·J E Sadler
Jun 1, 2000·The Journal of Biological Chemistry·A KatsumiJ E Sadler
Mar 29, 2001·Proceedings of the National Academy of Sciences of the United States of America·C V DenisD D Wagner
Oct 18, 2002·Current Opinion in Cell Biology·Peter ArvanRegina Kuliawat
Oct 1, 1964·The Journal of Cell Biology·E R WEIBEL, G E PALADE
Jul 21, 2004·Journal of Computational Chemistry·Eric F PettersenThomas E Ferrin
Aug 28, 2004·Blood·Sandra L HaberichterRobert R Montgomery
Sep 24, 2004·The Journal of Biological Chemistry·Angie R Purvis, J Evan Sadler
Sep 25, 2004·Protein Science : a Publication of the Protein Society·Hannes FischerAldo F Craievich
Oct 4, 2005·The Journal of Clinical Investigation·David G MottoDavid Ginsburg
Sep 9, 2006·American Journal of Respiratory Cell and Molecular Biology·Juan Perez-Vilar
Sep 29, 2006·Molecular Biology of the Cell·Jacqueline A SobotaRichard E Mains
May 31, 2007·Journal of Cell Science·Helen L ZennerDaniel F Cutler
Sep 25, 2007·Journal of Structural Biology·K M ValentijnA J Koster
Sep 27, 2007·Proceedings of the National Academy of Sciences of the United States of America·Angie R PurvisJ Evan Sadler

❮ Previous
Next ❯

Citations

Oct 7, 2009·Proceedings of the National Academy of Sciences of the United States of America·John A BerrimanPeter B Rosenthal
Mar 28, 2012·Proceedings of the National Academy of Sciences of the United States of America·Daniel AmbortGunnar C Hansson
Sep 8, 2011·The Journal of Biological Chemistry·Karen De CeunynckKaren Vanhoorelbeke
Nov 6, 2012·Cold Spring Harbor Perspectives in Medicine·Daniel AmbortGunnar C Hansson
Sep 29, 2009·American Journal of Physiology. Lung Cellular and Molecular Physiology·Mehmet KesimerJohn K Sheehan
Oct 27, 2009·American Journal of Physiology. Lung Cellular and Molecular Physiology·Paul M Quinton
May 27, 2008·Blood·Jan Voorberg
Feb 18, 2009·Blood·Daniel F Cutler
Feb 26, 2011·World Journal of Gastroenterology : WJG·Franco ScaldaferriRaimondo De Cristofaro
Jul 24, 2015·International Journal of Oncology·Werner Hoffmann
May 24, 2012·Seminars in Nephrology·David Motto
Jan 21, 2016·Proceedings of the National Academy of Sciences of the United States of America·Jochen P MüllerMartin Benoit
Nov 11, 2008·Journal of Molecular Biology·Ying A WangEdward H Egelman
Jul 28, 2009·Journal of Thrombosis and Haemostasis : JTH·J E Sadler
May 28, 2008·Journal of Thrombosis and Haemostasis : JTH·B M Luken
Feb 5, 2009·Journal of Thrombosis and Haemostasis : JTH·S L HaberichterJ C Gill
Feb 13, 2013·Journal of Thrombosis and Haemostasis : JTH·K M Valentijn, J Eikenboom
Aug 23, 2011·The EMBO Journal·Yan-Feng ZhouTimothy A Springer
Aug 23, 2012·Haemophilia : the Official Journal of the World Federation of Hemophilia·M BlombäckD Lillicrap
Aug 4, 2011·Journal of Thrombosis and Haemostasis : JTH·T A Springer
Aug 22, 2012·Journal of Thrombosis and Haemostasis : JTH·J W WangJ Eikenboom
Oct 7, 2011·The EMBO Journal·Volker Gerke
Sep 10, 2013·Journal of Thrombosis and Haemostasis : JTH·M J MourikJ Eikenboom
Aug 12, 2014·British Journal of Haematology·Dafna J GroeneveldJeroen Eikenboom
May 13, 2014·Journal of Molecular Biology·Harriet E NilssonHans Hebert
Jun 15, 2014·Blood·Timothy A Springer
Oct 25, 2012·Blood·Karen De CeunynckKaren Vanhoorelbeke
Apr 12, 2012·Blood·Yan-Feng ZhouTimothy A Springer

❮ Previous
Next ❯

Related Concepts

Related Feeds

Blood Clotting Disorders

Thrombophilia includes conditions with increased tendency for excessive blood clotting. Blood clotting occurs when the body has insufficient amounts of specialized proteins that make blood clot and stop bleeding. Here is the latest research on blood clotting disorders.