{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,20]],"date-time":"2026-10-20T04:38:56Z","timestamp":1792471136362,"version":"4.5.0"},"reference-count":89,"publisher":"Wiley","issue":"20","license":[{"start":{"date-parts":[[2026,5,2]],"date-time":"2026-05-02T00:00:00Z","timestamp":1777680000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,5,2]],"date-time":"2026-05-02T00:00:00Z","timestamp":1777680000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["febs.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The FEBS Journal"],"published-print":{"date-parts":[[2026,10]]},"abstract":"<jats:p>\n                    Fragile X messenger ribonucleoprotein 1 (FMRP) is a multidomain RNA\u2010binding protein highly expressed in neurons. It comprises a structured N\u2010terminal region (NTR) containing five RNA\/protein interaction domains and a large intrinsically disordered C\u2010terminal region. A limited number of fragile X syndrome (FXS)\u2010associated point mutations have been identified in the NTR, leading to the expression of mutated protein variants. Here, we show that the destabilizing effects of these mutations on the NTR region are less severe than those previously observed in the isolated domains, suggesting the presence of inter\u2010domain interactions that stabilize the overall NTR architecture. Moreover, we demonstrate that the NTR structured region has an intrinsic propensity to undergo liquid\u2013liquid phase separation (LLPS) and amyloid fibril formation\n                    <jats:italic>in vitro<\/jats:italic>\n                    , depending on protein concentration, and we characterize how three FXS\u2010associated mutations (R138Q, G266E, and I304N) affect these processes. We show that the mutations either destabilize the entire NTR (G266E\/I304N), markedly affect the kinetics of LLPS and suppress the droplet liquid nature (R138Q\/G266E), or promote solid or gel\u2010like non\u2010amyloid aggregation (G266E), thus providing mechanistic insights into how they may alter protein function, contributing to the pathogenic mechanism. These findings suggest that the interplay between protein stability, LLPS, and fibrillization is finely regulated and may be critical for understanding FMRP function and its dysfunction in disease.\n                  <\/jats:p>","DOI":"10.1111\/febs.70564","type":"journal-article","created":{"date-parts":[[2026,5,2]],"date-time":"2026-05-02T12:05:16Z","timestamp":1777723516000},"page":"6155-6175","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Unraveling\n                    <i>in vitro<\/i>\n                    phase separation and aggregation properties of the structured region of\n                    <scp>FMRP<\/scp>\n                    and the impact of Fragile X syndrome\u2010linked mutations"],"prefix":"10.1111","volume":"293","author":[{"given":"Flavia","family":"Catalano","sequence":"first","affiliation":[{"name":"Institute of Molecular Biology and Pathology National Research Council of Italy  Rome 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