A covalent oxidoreductase intermediate in propeptide-dependent von Willebrand factor multimerization.

The Journal of Biological Chemistry
Angie R Purvis, J Evan Sadler

Abstract

The assembly of von Willebrand factor multimers in the Golgi apparatus requires D1D2 domains of the von Willebrand factor propeptide, which may act as an oxidoreductase to promote disulfide bond formation or rearrangement between two D3 domains in the mature subunit. This mechanism predicts that the propeptide should form a transient intrachain disulfide bond with the D3 domain before multimerization. Such an intermediate was detected using truncated subunits that simplify the analysis of the multimerization process. When only the D1D2D'D3 region of von Willebrand factor was expressed in baby hamster kidney cells, the propeptide and D'D3 formed an intrachain disulfide-linked species in the endoplasmic reticulum that could be identified by two-dimensional gel electrophoresis after cleavage with thrombin or furin. This intermediate rearranged in the Golgi to form free propeptide and D'D3 dimers that were secreted. A similar intracellular disulfide-linked species was identified in cells expressing the propeptide and D'D3 as separate proteins and in cells expressing full-length von Willebrand factor. These results support a model in which the propeptide acts as an oxidoreductase to promote von Willebrand factor multimerization in t...Continue Reading

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Citations

Jan 10, 2008·Proceedings of the National Academy of Sciences of the United States of America·Ren-Huai HuangJ Evan Sadler
Oct 7, 2009·Proceedings of the National Academy of Sciences of the United States of America·John A BerrimanPeter B Rosenthal
Nov 18, 2011·Blood Coagulation & Fibrinolysis : an International Journal in Haemostasis and Thrombosis·Md Imtaiyaz HassanFaizan Ahmad
Oct 17, 2012·Journal of Hematology & Oncology·Hailong YuanQing Zhang
Sep 27, 2007·Proceedings of the National Academy of Sciences of the United States of America·Angie R PurvisJ Evan Sadler
Jul 24, 2015·International Journal of Oncology·Werner Hoffmann
Aug 17, 2005·Journal of Thrombosis and Haemostasis : JTH·J E Sadler
Jul 28, 2009·Journal of Thrombosis and Haemostasis : JTH·J E Sadler
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
Sep 10, 2013·Biophysical Journal·Svenja LippokJoachim O Rädler
Dec 23, 2016·Hämostaseologie·Marjon Mourik, Jeroen Eikenboom
Feb 14, 2014·Expert Review of Hematology·Sameh MikhailAmer Zeidan
Mar 31, 2007·The Journal of Biological Chemistry·Lindsay M RickettsElaine M Majerus
Feb 1, 2017·Hämostaseologie·Maria A Brehm
Feb 16, 2021·Hämostaseologie·Orla Rawley, David Lillicrap
Dec 22, 2007·Journal of Cell Science·Daniel J MetcalfDaniel F Cutler
Apr 30, 2021·Trauma Surgery & Acute Care Open·Taleen A MacArthurMyung S Park

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