{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,26]],"date-time":"2026-08-26T19:59:33Z","timestamp":1787774373151,"version":"build-2784847793"},"update-to":[{"DOI":"10.1371\/journal.ppat.1011953","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2024,2,15]],"date-time":"2024-02-15T00:00:00Z","timestamp":1707955200000}}],"reference-count":55,"publisher":"Public Library of Science (PLoS)","issue":"2","license":[{"start":{"date-parts":[[2024,2,5]],"date-time":"2024-02-05T00:00:00Z","timestamp":1707091200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["31971126"],"award-info":[{"award-number":["31971126"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["U20A20135"],"award-info":[{"award-number":["U20A20135"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["32301011"],"award-info":[{"award-number":["32301011"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"name":"National Program on Key Research Project of China","award":["2020YFA0707500"],"award-info":[{"award-number":["2020YFA0707500"]}]},{"DOI":"10.13039\/501100002858","name":"China Postdoctoral Science Foundation","doi-asserted-by":"publisher","award":["BX2021165"],"award-info":[{"award-number":["BX2021165"]}],"id":[{"id":"10.13039\/501100002858","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.plospathogens.org"],"crossmark-restriction":false},"short-container-title":["PLoS Pathog"],"abstract":"<jats:p>Carbonic anhydrase IV (Car4) is a newly identified receptor that allows adeno-associated virus (AAV) 9P31 to cross the blood-brain barrier and achieve efficient infection in the central nervous system (CNS) in mouse models. However, the molecular mechanism by which engineered AAV capsids with 7-mer insertion in the variable region (VR) VIII recognize these novel cellular receptors is unknown. Here we report the cryo-EM structures of AAV9P31 and its complex with <jats:italic>Mus musculus<\/jats:italic> Car4 at atomic resolution by utilizing the block-based reconstruction (BBR) method. The structures demonstrated that Car4 binds to the protrusions at 3-fold axes of the capsid. The inserted 7-mer extends into a hydrophobic region near the catalytic center of Car4 to form stable interactions. Mutagenesis studies also identified the key residues in Car4 responsible for the AAV9P31 interaction. These findings provide new insights into the novel receptor recognition mechanism of AAV generated by directed evolution and highlight the application of the BBR method to studying the virus-receptor molecular mechanism.<\/jats:p>","DOI":"10.1371\/journal.ppat.1011953","type":"journal-article","created":{"date-parts":[[2024,2,5]],"date-time":"2024-02-05T18:35:29Z","timestamp":1707158129000},"page":"e1011953","update-policy":"https:\/\/doi.org\/10.1371\/journal.ppat.corrections_policy","source":"Crossref","is-referenced-by-count":15,"title":["Structural basis of the recognition of adeno-associated virus by the neurological system-related receptor carbonic anhydrase 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Whitney","year":"1982","journal-title":"J Biol Chem"},{"issue":"1","key":"ppat.1011953.ref031","doi-asserted-by":"crossref","first-page":"360","DOI":"10.1046\/j.1471-4159.1994.63010360.x","article-title":"Up-regulation of carbonic anhydrase isozyme IV in CNS myelin of mice genetically deficient in carbonic anhydrase II","volume":"63","author":"LP Brion","year":"1994","journal-title":"J Neurochem"},{"key":"ppat.1011953.ref032","doi-asserted-by":"crossref","first-page":"195","DOI":"10.1111\/j.1749-6632.1984.tb12333.x","article-title":"Properties of membrane-bound carbonic anhydrase","volume":"429","author":"PJ Wistrand","year":"1984","journal-title":"Ann N Y Acad Sci"},{"issue":"7","key":"ppat.1011953.ref033","doi-asserted-by":"crossref","first-page":"855","DOI":"10.1177\/002215549804600709","article-title":"Localization of carbonic anhydrase IV in rat and human heart muscle","volume":"46","author":"S Sender","year":"1998","journal-title":"J Histochem Cytochem"},{"issue":"7","key":"ppat.1011953.ref034","doi-asserted-by":"crossref","first-page":"2716","DOI":"10.1073\/pnas.88.7.2716","article-title":"Localization of carbonic anhydrase IV in a specific capillary bed of the human eye","volume":"88","author":"GS Hageman","year":"1991","journal-title":"Proc Natl Acad Sci U S A"},{"issue":"2","key":"ppat.1011953.ref035","doi-asserted-by":"crossref","first-page":"211","DOI":"10.1046\/j.1365-201x.1999.00478.x","article-title":"Carbonic anhydrase IV activity is localized on the exterior surface of human erythrocytes","volume":"165","author":"PJ Wistrand","year":"1999","journal-title":"Acta Physiol Scand"},{"key":"ppat.1011953.ref036","article-title":"Primate-conserved Carbonic Anhydrase IV and murine-restricted Ly6c1 are new targets for crossing the blood-brain barrier","author":"TF Shay","year":"2023","journal-title":"bioRxiv"},{"key":"ppat.1011953.ref037","doi-asserted-by":"crossref","DOI":"10.7554\/eLife.44707","article-title":"Structure 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Matsuzaki","year":"2018","journal-title":"Neurosci Lett"},{"issue":"41","key":"ppat.1011953.ref043","doi-asserted-by":"crossref","first-page":"20462","DOI":"10.1073\/pnas.1904918116","article-title":"Transferrin receptor binds virus capsid with dynamic motion","volume":"116","author":"H Lee","year":"2019","journal-title":"Proc Natl Acad Sci U S A"},{"issue":"8","key":"ppat.1011953.ref044","doi-asserted-by":"crossref","first-page":"e1501929","DOI":"10.1126\/sciadv.1501929","article-title":"The novel asymmetric entry intermediate of a picornavirus captured with nanodiscs","volume":"2","author":"H Lee","year":"2016","journal-title":"Science advances"},{"issue":"7882","key":"ppat.1011953.ref045","doi-asserted-by":"crossref","first-page":"672","DOI":"10.1038\/s41586-021-03963-9","article-title":"Structure of Venezuelan equine encephalitis virus in complex with the LDLRAD3 receptor","volume":"598","author":"K 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