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However, a critical gap exists between the oligomeric state of hnRNP A2\/B1 and its function as a nuclear DNA sensor. To address this gap, we generated full-length hnRNP A2\/B1 and three domain-truncated variants (\u25b3NLS, RRM-PrLD, RRM-RGG) using SUMO\/MBP fusion expression systems. To define the nucleic acid binding and oligomeric properties of these variants, we combined SEC with EMSA and ITC. These analyses revealed that full-length hnRNP A2\/B1 forms soluble amorphous aggregates, whereas the truncated variants exist as stable homogeneous monomers under in vitro solution conditions. Additionally, results demonstrated that the RRM-RGG (15\u2013250) variant binds to ssDNA but not dsDNA. Notably, SEC combined with CD and AUC confirmed that RRM-RGG (15\u2013250) truncations undergo homodimerization induced by 12nt and 22nt Guanine quadruplex (G4) structure enriched ssDNA, which is abundant in the genomes of diverse viruses. Structure predictions revealed that the C-terminal PrLD, and NLS domain are intrinsically disordered, a feature potentially underlying the protein\u2019s aggregation propensity and crystallization recalcitrance. NPDock simulations demonstrated that G4-structured ssDNA binds and stabilizes the RRM-RGG (15\u2013250) truncation via non-conserved key residues that are distinct from those of other hnRNP family members. This work provides a biophysical basis for hypothesizing that G4-structured ssDNA-dependent dimerization may contribute to the protein\u2019s antiviral function, and establishes a biophysical framework to guide future investigations into the protein\u2019s antiviral mechanism and the design of rational targeted inhibitors.<\/jats:p>","DOI":"10.1038\/s41598-026-44646-7","type":"journal-article","created":{"date-parts":[[2026,3,26]],"date-time":"2026-03-26T08:32:16Z","timestamp":1774513936000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Molecular recognition and induced dimerization of hnRNP A2\/B1 truncations by G-quadruplex single strand DNA"],"prefix":"10.1038","volume":"16","author":[{"given":"Dilidaer","family":"Shahatibieke","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaohui","family":"Tang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xuanfang","family":"Zheng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yue","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Abudoureyimu","family":"Abula","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,3,26]]},"reference":[{"key":"44646_CR1","doi-asserted-by":"publisher","first-page":"1497938","DOI":"10.3389\/fcvm.2025.1497938","volume":"12","author":"Y Wei","year":"2025","unstructured":"Wei, Y. et al. 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