Biochemistry

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Science  01 Feb 2008:
Vol. 319, Issue 5863, pp. 549
DOI: 10.1126/science.319.5863.549d

At sites of vascular injury, a large multimeric glycoprotein (von Willebrand's factor; VWF) secreted from endothelial cells binds platelets to form a hemostatic plug. Within endothelial cells, VWF multimers pack as ordered tubules into cigar-shaped secretory granules called Weibel-Palade bodies; this packaging is essential for orderly secretion of VWF filaments.

Using only the N-terminal propeptide D1D2 and the adjacent D'D3 domains, Huang et al. have reconstituted in vitro the formation of Weibel-Palade body-like tubules, which occurs at low pH (6.2) and in the presence of Ca2+. Electron microscopic reconstruction showed that the tubules formed a right-handed helix with 4.2 units per turn, with the repeating unit containing a D'D3 dimer and two propeptides. The authors suggest that these domains form the core of the tubules, with the remaining C-terminal portion of the protein decorating the outside. In the Golgi, the relatively acidic pH and high Ca2+ would increase the interaction between D1D2 and D'D3, juxtaposing the two D3 domains and facilitating intersubunit disulfide bond formation and multimerization. The higher pH in blood would weaken these interactions and allow the helical tubules to unfurl without tangling. — VV

Proc. Natl. Acad. Sci. U.S.A. 105, 482 (2008).

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