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Previously, a 57-amino acid loop in the biofilm-specific adhesin Bap1 (Bap1-57aa) has been identified as a key contributor to the adhesion of\n                    <jats:italic>V. cholerae<\/jats:italic>\n                    biofilms to various surfaces including lipid membranes. However, the mechanism underlying its interaction with lipids, as well as its secondary structures, remain unresolved. Here, we combined biophysical, computational, and genetic approaches to elucidate the molecular mechanism of how this adhesive peptide interacts with lipids and lipid-coated surfaces. We found that a central aromatic-rich motif anchors the peptide to lipid bilayers while peripheral pseudo repeats enhance binding through avidity. Surprisingly, the core motif undergoes a lipid-induced conformational transition into a \u03b2-hairpin, enabling robust membrane insertion. We confirmed these findings both\n                    <jats:italic>in vitro<\/jats:italic>\n                    and in the biofilm context. Moreover, we demonstrated that the adhesive peptide can adhere to model host surfaces and is sensitive to membrane curvature. Finally, we show that the biofilm-derived peptide is found in several other\n                    <jats:italic>Vibrio<\/jats:italic>\n                    species, and its sequence is well-conserved. Our results provide molecular insight into biofilm adhesion and may lead to new strategies for targeted biofilm removal, as well as the design of bioinspired underwater adhesives.\n                  <\/jats:p>","DOI":"10.1371\/journal.ppat.1013990","type":"journal-article","created":{"date-parts":[[2026,2,19]],"date-time":"2026-02-19T18:42:27Z","timestamp":1771526547000},"page":"e1013990","update-policy":"https:\/\/doi.org\/10.1371\/journal.ppat.corrections_policy","source":"Crossref","is-referenced-by-count":7,"title":["Conformations and sequence determinants in the lipid binding of an adhesive peptide derived from Vibrio cholerae biofilms"],"prefix":"10.1371","volume":"22","author":[{"given":"Xin","family":"Huang","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ramesh","family":"Prasad","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sarvagya","family":"Saluja","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yiyan","family":"Yang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qi","family":"Yan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sydney 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M.","family":"Davis","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaofang","family":"Jiang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huan-Xiang","family":"Zhou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2773-0348","authenticated-orcid":true,"given":"Jing","family":"Yan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2026,2,19]]},"reference":[{"issue":"1","key":"ppat.1013990.ref001","doi-asserted-by":"crossref","first-page":"275","DOI":"10.1146\/annurev-biophys-070124-092816","article-title":"Membrane association of intrinsically disordered proteins","volume":"54","author":"M MacAinsh","year":"2025","journal-title":"Annu Rev 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