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-Structure paper
タイトル | Assembly of von Willebrand factor tubules with in vivo helical parameters requires A1 domain insertion. |
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ジャーナル・号・ページ | Blood, Vol. 140, Issue 26, Page 2835-2843, Year 2022 |
掲載日 | 2022年12月29日 |
著者 | Gabriel Javitt / Noa Yeshaya / Lev Khmelnitsky / Deborah Fass / |
PubMed 要旨 | The von Willebrand factor (VWF) glycoprotein is stored in tubular form in Weibel-Palade bodies (WPBs) before secretion from endothelial cells into the bloodstream. The organization of VWF in the ...The von Willebrand factor (VWF) glycoprotein is stored in tubular form in Weibel-Palade bodies (WPBs) before secretion from endothelial cells into the bloodstream. The organization of VWF in the tubules promotes formation of covalently linked VWF polymers and enables orderly secretion without polymer tangling. Recent studies have described the high-resolution structure of helical tubular cores formed in vitro by the D1D2 and D'D3 amino-terminal protein segments of VWF. Here we show that formation of tubules with the helical geometry observed for VWF in intracellular WPBs requires also the VWA1 (A1) domain. We reconstituted VWF tubules from segments containing the A1 domain and discovered it to be inserted between helical turns of the tubule, altering helical parameters and explaining the increased robustness of tubule formation when A1 is present. The conclusion from this observation is that the A1 domain has a direct role in VWF assembly, along with its known activity in hemostasis after secretion. |
リンク | Blood / PubMed:36179246 / PubMed Central |
手法 | EM (らせん対称) |
解像度 | 3.2 - 5.74 Å |
構造データ | EMDB-14998, PDB-7zwh: EMDB-15004: VWF tubules of D1D2 and D'A1A2A3 EMDB-15005: VWF tubules od D1D2D'D3A1 domains with an R763G furin cleavage site mutation |
化合物 | ChemComp-NAG: ChemComp-CA: |
由来 |
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キーワード | BLOOD CLOTTING / helical / tubule / vwa1 / a1 domain / a1 / vwf / von willebrand factor / helical tubule |