{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,28]],"date-time":"2026-10-28T03:13:53Z","timestamp":1793157233012,"version":"4.5.0"},"reference-count":47,"publisher":"American Society of Hematology","issue":"12","license":[{"start":{"date-parts":[[2022,7,1]],"date-time":"2022-07-01T00:00:00Z","timestamp":1656633600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/legalcode"}],"content-domain":{"domain":["ashpublications.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2022,9,22]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>von Willebrand factor (VWF) is an adhesive glycoprotein that circulates in the blood as disulfide-linked concatemers and functions in primary hemostasis. The loss of long VWF concatemers is associated with the excessive bleeding of type 2A von Willebrand disease (VWD). Formation of the disulfide bonds that concatemerize VWF requires VWF to self-associate into helical tubules, yet how the helical tubules template intermolecular disulfide bonds is not known. Here, we report electron cryomicroscopy (cryo-EM) structures of VWF tubules before and after intermolecular disulfide bond formation. The structures provide evidence that VWF tubulates through a charge\u2013neutralization mechanism and that the A1 domain enhances tubule length by crosslinking successive helical turns. In addition, the structures reveal disulfide states before and after disulfide bond-mediated concatemerization. The structures and proposed assembly mechanism provide a foundation to rationalize VWD-causing mutations.<\/jats:p>","DOI":"10.1182\/blood.2022016467","type":"journal-article","created":{"date-parts":[[2022,7,1]],"date-time":"2022-07-01T20:01:12Z","timestamp":1656705672000},"page":"1419-1430","update-policy":"https:\/\/doi.org\/10.1182\/blood.2019cm0000","source":"Crossref","is-referenced-by-count":29,"title":["Structures of VWF tubules before and after concatemerization reveal a mechanism of disulfide bond exchange"],"prefix":"10.1182","volume":"140","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1179-717X","authenticated-orcid":false,"given":"Jacob R.","family":"Anderson","sequence":"first","affiliation":[{"name":"1Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, MA;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9603-7788","authenticated-orcid":false,"given":"Jing","family":"Li","sequence":"additional","affiliation":[{"name":"1Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, MA;"},{"name":"2Program in Cellular and Molecular Medicine, Boston Children\u2019s Hospital, Boston, MA; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6627-2904","authenticated-orcid":false,"given":"Timothy A.","family":"Springer","sequence":"additional","affiliation":[{"name":"1Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, MA;"},{"name":"3Department of Pediatrics, Harvard Medical School, Boston, MA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0021-0476","authenticated-orcid":false,"given":"Alan","family":"Brown","sequence":"additional","affiliation":[{"name":"1Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, MA;"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"234","reference":[{"issue":"21","key":"2022092215284693800_B1","doi-asserted-by":"crossref","first-page":"2067","DOI":"10.1056\/NEJMra1601561","article-title":"von Willebrand\u2019s disease","volume":"375","author":"Leebeek","year":"2016","journal-title":"N Engl J Med."},{"issue":"1","key":"2022092215284693800_B2","doi-asserted-by":"crossref","first-page":"93","DOI":"10.1111\/j.1365-2141.1989.tb00226.x","article-title":"Binding of von Willebrand factor to glycoproteins Ib and IIb\/IIIa complex: affinity is related to multimeric size","volume":"73","author":"Federici","year":"1989","journal-title":"Br J Haematol."},{"issue":"4","key":"2022092215284693800_B3","doi-asserted-by":"crossref","first-page":"2065","DOI":"10.1016\/S0021-9258(18)32879-5","article-title":"Biosynthesis of von Willebrand protein by human endothelial cells. 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