The von Willebrand factor D'D3 assembly and structural principles for factor VIII binding and concatemer biogenesis.

摘要: D assemblies make up half of the von Willebrand factor (VWF), yet are unknown structure. D1 and D2 in prodomain D'D3 mature VWF at Golgi pH form helical tubules Weibel Palade bodies template dimerization D3 through disulfides to ultralong concatemers. forms binding site for VIII. The crystal structure monomeric with cysteine residues required mutated alanine was determined an endoplasmic reticulum (ER)-like pH. smaller C8-3, TIL3 (trypsin inhibitor-like 3), E3 modules pack specific interfaces as they wind around larger, N-terminal, Ca2+-binding domain (VWD) 3 module a wedge shape. D' its TIL' E' projects away from D3. 2 cysteines implicated buried, providing mechanism protecting them against premature disulfide linkage ER, where intrachain linkages formed. requires co-association D2, Ca2+, Golgi-like acidic Associated structural rearrangements C8-3 expose linkage. Our provides insight into many disease mutations, including those that diminish VIII binding, which suggest binds not only N-terminal distal but also extends across 1 side organizing principle assembly has implications other construction higher-order, disulfide-linked both mucins.