{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T21:19:24Z","timestamp":1792790364545,"version":"4.5.0"},"posted":{"date-parts":[[2026,9,24]]},"group-title":"Neuroscience","reference-count":54,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T00:00:00Z","timestamp":1790208000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/www.biorxiv.org\/about\/FAQ#license"}],"funder":[{"award":["R01 MH130428"],"award-info":[{"award-number":["R01 MH130428"]}],"id":[{"id":"https:\/\/ror.org\/04xeg9z08","id-type":"ROR","asserted-by":"publisher"}]},{"award":["R01 MH099114"],"award-info":[{"award-number":["R01 MH099114"]}],"id":[{"id":"https:\/\/ror.org\/04xeg9z08","id-type":"ROR","asserted-by":"publisher"}]},{"award":["R01 NS115471"],"award-info":[{"award-number":["R01 NS115471"]}],"id":[{"id":"https:\/\/ror.org\/01s5ya894","id-type":"ROR","asserted-by":"publisher"}]},{"name":"National Eye Institute","award":["R01 EY032506"],"award-info":[{"award-number":["R01 EY032506"]}],"id":[{"id":"https:\/\/ror.org\/03wkg3b53","id-type":"ROR","asserted-by":"crossref"}]},{"award":["R01 AG078796"],"award-info":[{"award-number":["R01 AG078796"]}],"id":[{"id":"https:\/\/ror.org\/049v75w11","id-type":"ROR","asserted-by":"publisher"}]},{"award":["S10 OD032464"],"award-info":[{"award-number":["S10 OD032464"]}],"id":[{"id":"https:\/\/ror.org\/01cwqze88","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2026,9,22]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                <jats:p>\n                  Pathological protein conformational remodeling is a key molecular feature of brain disorders. However, conventional approaches to understand the changes in potein conformation are targeted and difficult to scale proteome-wide analysis. Emerging mass spectrometry-based structural proteomic methods broaden coverage but often involve complex workflows and trade- offs between labeling efficiency and preservation of the\n                  <jats:italic>in vivo<\/jats:italic>\n                  molecular state. Thus, quantitative analysis of proteome-wide structural remodeling remains limited. Here we present Brain Landscape In Situ Crosslinking Mass Spectrometry (BLIS-XL-MS), an experimental and computational framework for analyzing protein and protein-complex remodeling in brain tissue. BLIS-XL-MS stabilizes the molecular state before secondary crosslinking, improves reagent accessibility through sectioning and permeabilization, and integrates quantitative crosslink analysis with structural and protein-interaction-network interpretation. Applied to brains from GluA1\n                  <jats:sup>A636T<\/jats:sup>\n                  knock-in mice, modeling a neurodevelopmental disorder, BLIS-XL-MS revealed coordinated remodeling of protein systems involved in AMPA receptor-trafficking, mitochondrial function and cell-death pathways. We demonstrate that BLIS-XL-MS provides a scalable framework for mapping disease-associated structural remodeling across the brain proteome.\n                <\/jats:p>","DOI":"10.64898\/2026.09.16.752161","type":"posted-content","created":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T21:05:45Z","timestamp":1790283945000},"source":"Crossref","is-referenced-by-count":0,"title":["Brain Landscape In Situ Crosslinking Mass Spectrometry (BLIS-XL-MS) Enables Global Analysis of Protein Structural Remodeling in the Brain"],"prefix":"10.64898","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5279-5034","authenticated-orcid":false,"given":"Yi-Zhi","family":"Wang","sequence":"first","affiliation":[{"name":"Department of Neurology, University Feinberg School of Medicine, Chicago, IL 60613"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jian","family":"Xu","sequence":"additional","affiliation":[{"name":"Department of Neuroscience, University Feinberg School of Medicine, 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