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In contrast, the secreted acid phosphatase (SAP) of\n                    <jats:italic>Leishmania<\/jats:italic>\n                    , one of the most abundant extracellular glycoproteins produced by the parasite and regarded as a major virulence factor in the neglected tropical disease leishmaniasis, exhibits fundamentally different behavior. Depending on the species, SAP forms either highly stable extracellular filaments or remains exclusively as globular particles, with no evidence of reversible interconversion. This binary assembly pattern is particularly intriguing given that SAP orthologs that differ in their ability to polymerize share a high degree of sequence conservation, leaving the molecular determinants of filament formation unknown. Here, we report the cryo\u2010EM structure of filamentous\n                    <jats:italic>Leishmania mexicana<\/jats:italic>\n                    SAP to a global resolution of 3.0\u2009\u00c5. The structure resolves the multilevel organization of the enzyme, from individual catalytic phosphatase domains and their unique substrate\u2010binding pockets to the formation of homodimeric protomers, the decoration with N\u2010linked glycans, and the supramolecular organization into filaments. At the core of the polymerization interface, we identified a unique \u03b2\u2010hairpin motif that has not been observed in any other phosphatase or enzyme filament, which provides exceptional filament stability. By integrating structural data with comparative sequence analysis and machine\u2010learning\u2010based structure predictions, we define the molecular basis for the species\u2010specific assembly behaviors observed across\n                    <jats:italic>Leishmania<\/jats:italic>\n                    SAPs. This work establishes the principles governing SAP filament formation and provides a framework for understanding its evolution, enzymatic function, and potential applications.\n                  <\/jats:p>","DOI":"10.1002\/pro.70591","type":"journal-article","created":{"date-parts":[[2026,4,21]],"date-time":"2026-04-21T04:57:13Z","timestamp":1776747433000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Structural basis of secreted acid phosphatase polymerization in the\n                    <i>Leishmania<\/i>\n                    parasite"],"prefix":"10.1002","volume":"35","author":[{"given":"Priyanka","family":"Bose","sequence":"first","affiliation":[{"name":"Department of Life Sciences Ben\u2010Gurion University of the Negev  Beer Sheva Israel"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Irit","family":"Dahan","sequence":"additional","affiliation":[{"name":"Department of Life Sciences Ben\u2010Gurion University of the Negev  Beer Sheva Israel"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alexander","family":"Upcher","sequence":"additional","affiliation":[{"name":"The Ilse Katz Institute for Nanoscale Science and Technology Ben\u2010Gurion University of the Negev  Beer Sheva Israel"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ran","family":"Zalk","sequence":"additional","affiliation":[{"name":"The Ilse Katz Institute for Nanoscale Science and Technology Ben\u2010Gurion University of the Negev  Beer Sheva Israel"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Iris","family":"Grossman\u2010Haham","sequence":"additional","affiliation":[{"name":"Department of Life Sciences Ben\u2010Gurion University of the Negev  Beer Sheva Israel"},{"name":"The Ilse Katz Institute for Nanoscale Science and Technology Ben\u2010Gurion University of the Negev  Beer Sheva 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