{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,7,18]],"date-time":"2026-07-18T13:02:46Z","timestamp":1784379766010,"version":"3.55.0"},"posted":{"date-parts":[[2026,7,15]]},"group-title":"Biochemistry","reference-count":69,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2026,7,15]],"date-time":"2026-07-15T00:00:00Z","timestamp":1784073600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100015326","name":"NIH Common Fund","doi-asserted-by":"crossref","award":["P01 GM072694"],"award-info":[{"award-number":["P01 GM072694"]}],"id":[{"id":"10.13039\/100015326","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2026,7,15]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                <jats:p>Neuroendocrine cells communicate with other cells by releasing neurotransmitters or hormones by exocytosis, which involves SNARE-mediated fusion between secretory vesicles and the plasma membranes of the secreting cells. In neurons two plasma membrane SNARE proteins, Syntaxin-1a and SNAP25, join with the vesicle membrane SNARE protein Synaptobrevin-2 to form a four-helix bundle, which drives membrane fusion. The assembly of these SNAREs, which is highly orchestrated in cells, has been intensely studied in solution using fragments of the SNARE proteins without their transmembrane domains or lipid anchors. However, in cell and model membranes, Syntaxin and SNAP25 are known to oligomerize and cluster, and little is known about how clustering affects their incorporation into SNARE complexes. In cells, the SM protein Munc18 has been implicated in aiding secretory vesicle docking and facilitating SNARE complex assembly through its interactions with Syntaxin.<\/jats:p>\n                <jats:p>To understand how Munc18 orchestrates SNARE complex assembly on membranes, we employed protein reconstitution in model membranes as well as biochemical and biophysical assays to show that lipid-dependent oligomerization of Syntaxin affects Munc18-Syntaxin binding and SNAP25 insertion into the plasma membrane acceptor SNARE complex. We showcase the consequences of the different modes of Munc18-Syntaxin and SNAP25 interaction on Syntaxin\u2019s oligomerization and orientation relative to the membrane surface, as well as on docking and fusion of purified insulin granules. We also determined low-resolution structures by cryoEM in nanodiscs and on the surface of proteoliposomes of membrane-bound assembly states of Munc18\/Syntaxin and Munc18\/Syntaxin\/SNAP25 complexes.<\/jats:p>","DOI":"10.64898\/2026.07.14.738512","type":"posted-content","created":{"date-parts":[[2026,7,15]],"date-time":"2026-07-15T11:40:14Z","timestamp":1784115614000},"source":"Crossref","is-referenced-by-count":0,"title":["Munc18 binds to and organizes membrane-bound acceptor Q-SNARE complexes in a fashion that depends on the membrane\u2019s lipid composition"],"prefix":"10.64898","author":[{"ORCID":"https:\/\/orcid.org\/0009-0009-3742-4214","authenticated-orcid":false,"given":"Weronika","family":"Tomaka","sequence":"first","affiliation":[{"name":"Center for Membrane and Cell Physiology, Department of Molecular Physiology and Biological Physics, University of Virginia, Charlottesville, VA 22908, 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Physiology, Department of Molecular Physiology and Biological Physics, University of Virginia, Charlottesville, VA 22908, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1674-4464","authenticated-orcid":false,"given":"Lukas K.","family":"Tamm","sequence":"additional","affiliation":[{"name":"Center for Membrane and Cell Physiology, Department of Molecular Physiology and Biological Physics, University of Virginia, Charlottesville, VA 22908, 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