The N’ terminus of Alpha-1 Giardin, a parasitic annexin orthologue, is essential for oligomerization and lipid-binding activity
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ABSTRACT: We present a functional analysis of alpha-giardins (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), 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 are regulated at PEC membranes. Together, our findings establish a mechanistic framework for annexin-mediated UPS in Giardia and provide structural insights relevant to parasite virulence and vaccine development.
INSTRUMENT(S):
ORGANISM(S): Giardia Intestinalis Assemblage A
DISEASE(S): Giardiasis
SUBMITTER:
Manfred Heller
LAB HEAD: Carmen Faso
PROVIDER: PXD074377 | Pride | 2026-06-11
REPOSITORIES: Pride
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