Cryo-EM structures of VWF tubules. (A) Domain arrangement of pro-VWF. Furin cleaves pro-VWF between D2 and D’ domains. Each VWF D domain has 4 modules (VWD, C8, TIL, and E8). (B) The tubule structure of 1 repeating unit shows a D’D3 dimer (marine and gray) docked in the central hole of a donut-shaped D1D2 dimer (cyan and pink). (C) The configuration of D1D2 fragment with each module colored differently. (D) The donut-shaped D1D2 dimer formed through D1:D2 interface. (E) The D’D3 dimers with 2 disulfide bonds (Cys1142-Cys1142’ and Cys1097-Cys1097’) in the interface. (F) Structure of tubule containing 2 repeating units. The 2 units are linked through the D2:D2 interface where D1D2 in 1 unit (gray) is expected to link with 1 D’D3 of the other unit (gray) in vivo. (G) Cryo-EM structure of tubule containing 8 repeating units packed as a right-hand helix with each unit colored differently. SP, signal peptide.