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Data from: The N’ terminus of Alpha-1 Giardin, a parasitic annexin orthologue, is essential for oligomerization and lipid-binding activity

Faso, Carmen1; Warmus, Dawid1; Wirdnam, Corina D.1; Balmer, Erina A.1; Muronzi, Tendai2; Heller, Manfred1; Tastan Bishop, Özlem2

Published Jun 22, 2026 on Dryad. https://doi.org/10.5061/dryad.02v6wwqk4

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Abstract

Annexins are Ca²⁺- and membrane-binding proteins conserved across eukaryotes and involved in diverse membrane-associated processes, including unconventional protein secretion (UPS). In the intestinal parasite Giardia lamblia, annexins are represented by a family of 21 proteins termed alpha-giardins (αGs), all of which lack classical signal peptides yet are detected at the parasite surface and in the secretome. Here, we present a comprehensive functional analysis of αGs, with a particular focus on α1-giardin (α1G), a leading vaccine candidate against giardiasis and a putative virulence-associated UPS substrate. We show that αGs localize to peripheral endocytic compartments (PECs-PVs), specialized endo-lysosomal organelles implicated in protein release, and engage in multiprotein complexes enriched in UPS substrates. Using lipid-binding assays, cross-linking mass spectrometry (XL-MS), and structural modelling, we define conserved and divergent features of αG membrane interactions. Focusing on α1G, we combine site-directed mutagenesis, confocal microscopy, and mass photometry to demonstrate a critical role for its short N-terminal region in oligomerization and membrane association. Integration of these data with molecular dynamics simulations reveals how α1G oligomeric state and membrane occupancy could be regulated at PECs-PVs membranes. Taken together, our findings provide structural insights relevant to parasite virulence and vaccine development and contribute to a mechanistic model for annexin-mediated UPS in Giardia.