Premium
A pH‐regulated dimeric bouquet in the structure of von Willebrand factor
Author(s) -
Zhou YanFeng,
Eng Edward T,
Nishida Noritaka,
Lu Chafen,
Walz Thomas,
Springer Timothy A
Publication year - 2011
Publication title -
the embo journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.484
H-Index - 392
eISSN - 1460-2075
pISSN - 0261-4189
DOI - 10.1038/emboj.2011.297
Subject(s) - von willebrand factor , biology , dimer , golgi apparatus , biogenesis , microbiology and biotechnology , biochemistry , biophysics , platelet , chemistry , gene , endoplasmic reticulum , immunology , organic chemistry
At the acidic pH of the trans ‐Golgi and Weibel–Palade bodies (WPBs), but not at the alkaline pH of secretion, the C‐terminal ∼1350 residues of von Willebrand factor (VWF) zip up into an elongated, dimeric bouquet. Six small domains visualized here for the first time between the D4 and cystine‐knot domains form a stem. The A2, A3, and D4 domains form a raceme with three pairs of opposed, large, flower‐like domains. N‐terminal VWF domains mediate helical tubule formation in WPBs and template N‐terminal disulphide linkage between VWF dimers, to form ultralong VWF concatamers. The dimensions we measure in VWF at pH 6.2 and 7.4, and the distance between tubules in nascent WPB, suggest that dimeric bouquets are essential for correct VWF dimer incorporation into growing tubules and to prevent crosslinking between neighbouring tubules. Further insights into the structure of the domains and flexible segments in VWF provide an overall view of VWF structure important for understanding both the biogenesis of ultralong concatamers at acidic pH and flow‐regulated changes in concatamer conformation in plasma at alkaline pH that trigger hemostasis.