Molecular basis for functional diversity among microbial Nep1-like proteins

• DOI: 10.1371/journal.ppat.1007951
• Publication Date: 2019-09-03T19:13:19Z
• Authors: Tea Lenarčič; Katja Pirc; Vesna Hodnik; Isabell Albert; Jure Borišek; Alessandra Magist...; Thorsten Nürnberger; Marjetka Podobnik; Gregor Anderluh
• Keywords: Obligate; Coxiella burnetii

Necrosis and ethylene-inducing peptide 1 (Nep1)-like proteins (NLPs) are secreted by several phytopathogenic microorganisms. They trigger necrosis in various eudicot plants upon binding to plant sphingolipid glycosylinositol phosphorylceramides (GIPC). Interestingly, HaNLP3 from the obligate biotroph oomycete Hyaloperonospora arabidopsidis does not induce necrosis. We determined crystal structure of showed that it adopts NLP fold. However, conformations loops surrounding GIPC headgroup-binding cavity differ those cytotoxic Pythium aphanidermatum NLPPya. Essential dynamics extracted μs-long molecular (MD) simulations reveals a limited conformational plasticity GIPC-binding relative toxic NLPs. This likely precludes GIPCs, which is underlying reason for lack toxicity. study mutations at key protein regions cause switch between non-toxic phenotypes within same scaffold. Altogether, these data provide evidence flexibility distinguishing trait NLPs highlight structural determinants potential functional diversification utilized biotrophic pathogens.