The many dimeric faces of Lys49 PLA₂-like proteins: Conformational plasticity and membrane binding drive functional dimer states.

ABSTRACT: Lys49 secreted phospholipase A₂-like proteins (sPLA₂s) are major myotoxins in viperid snake venoms, causing rapid muscle damage in envenomation. Beyond their clinical relevance, these small non-catalytic proteins provide a model to study how quaternary structure and conformational dynamics enable catalysis-independent membrane disruption. Using site-directed mutagenesis, fluorescence anisotropy, and extensive atomistic and coarse-grained molecular dynamics simulations, we characterized the conformational landscape of Bothropstoxin-I (BthTx-I), a prototypical Lys49 sPLA₂-like protein. Our results show that compact and extended dimers coexist in solution but differ in flexibility, with only the extended dimer reproducing experimental FRET efficiencies across

SUBMITTER: Lima DCA 

PROVIDER: S-EPMC12817292 | biostudies-literature | 2026 Feb

REPOSITORIES: biostudies-literature