{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,9]],"date-time":"2025-10-09T01:07:20Z","timestamp":1759972040443,"version":"build-2065373602"},"reference-count":40,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2024,12,23]],"date-time":"2024-12-23T00:00:00Z","timestamp":1734912000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100020595","name":"National Science and Technology Council","doi-asserted-by":"publisher","award":["113-2923-M-001-001-MY3"],"award-info":[{"award-number":["113-2923-M-001-001-MY3"]}],"id":[{"id":"10.13039\/100020595","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100009122","name":"Ministry of Higher Education and Scientific Research","doi-asserted-by":"publisher","award":["MOE 111BRC\u2212B408","112BRC\u2212B408","113BRC\u2212B408"],"award-info":[{"award-number":["MOE 111BRC\u2212B408","112BRC\u2212B408","113BRC\u2212B408"]}],"id":[{"id":"10.13039\/100009122","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["aces.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Chemistry \u0097 An Asian Journal"],"published-print":{"date-parts":[[2025,2,17]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Transthyretin (TTR), a homo\u2010tetrameric protein encoded by the <jats:italic>TTR<\/jats:italic> gene, can lead to amyloid diseases when destabilized by mutations. The <jats:italic>TTR<\/jats:italic>\u2010Ala97Ser (A97S) mutation is the predominant pathogenic variant found in Han\u2010Taiwanese patients and is associated with late\u2010onset familial amyloid polyneuropathy (FAP), which presents a rapid progression of symptoms affecting peripheral nerves and the heart. In this study, we combined nuclear magnetic resonance (NMR) spectroscopy and X\u2010ray crystallography to investigate how the A97S mutation impacts the structure and dynamics of TTR. Previous X\u2010ray analyses indicated that the FG loop exhibits increased flexibility due to the mutation, evidenced by missing electron density and a reduced number of hydrogen bonds. Our NMR hydrogen\u2010deuterium (H\/D) exchange experiments provided additional insights, revealing that inter\u2010residue hydrogen bonds among the FG loop residues are unstable in both wild\u2010type (WT) and A97S TTR. Notably, the hydrogen bonds between G67 and S97 are unstable, influencing the stability of adjacent loops. This elongation of the FG loop is believed to contribute to increased flexibility and enhanced water\u2010protein proton exchange, as observed in NMR relaxation and chemical exchange experiments. Our findings offer a comprehensive understanding of how the A97S mutation affects TTR structure and dynamics, providing new insights into its amyloidogenicity.<\/jats:p>","DOI":"10.1002\/asia.202401438","type":"journal-article","created":{"date-parts":[[2024,12,13]],"date-time":"2024-12-13T01:30:17Z","timestamp":1734053417000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["The Structural and Dynamic Insights into the Ala97Ser Amyloidogenic Mutation in Transthyretin"],"prefix":"10.1002","volume":"20","author":[{"ORCID":"https:\/\/orcid.org\/0009-0004-0826-2686","authenticated-orcid":false,"given":"Yu\u2010Chen","family":"Feng","sequence":"first","affiliation":[{"name":"Institute of Atomic and Molecular Sciences, Academia Sinica  No. 1, Sec. 4, Roosevelt Rd., Daan Dist. Taipei 106319 Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sashank","family":"Agrawal","sequence":"additional","affiliation":[{"name":"Institute of Atomic and Molecular Sciences, Academia Sinica  No. 1, Sec. 4, Roosevelt Rd., Daan Dist. Taipei 106319 Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chin\u2010Hao","family":"Yang","sequence":"additional","affiliation":[{"name":"Institute of Atomic and Molecular Sciences, Academia Sinica  No. 1, Sec. 4, Roosevelt Rd., Daan Dist. Taipei 106319 Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hao\u2010Chih","family":"Chang","sequence":"additional","affiliation":[{"name":"School of Medicine National Yang Ming Chiao Tung University No. 155, Sec. 2  Linong St., Beitou Dist. Taipei 112304 Taiwan"},{"name":"Division of Cardiology Department of Medicine Taipei Veterans General Hospital No. 201, Sec. 2  Shipai Rd., Beitou Dist. 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