Structural highlights
Publication Abstract from PubMedFrancisella tularensis is the etiological agent of tularemia, or rabbit fever. While F. tularensis is a recognized biothreat agent with broad and expanding geographical range, its mechanism of infection and environmental persistence remain poorly understood. Previously, we identified seven F. tularensis proteins that induce a rapid encystment phenotype (REP) in the free-living amoeba, Acanthamoeba castellanii. Encystment is essential to the pathogen's long-term intracellular survival in amoeba. Here, we characterize the cellular and molecular function of REP34, a REP protein of mass 34 kDa. A REP34 knockout strain of F. tularensis has a reduced ability to both induce encystment in A. castellanii and invade human macrophages. We determined the crystal structure of REP34 to 2.05-A resolution and demonstrate robust carboxypeptidase B-like activity for the enzyme. REP34 is a zinc-containing monomeric protein with close structural homology to the metallocarboxypeptidase family of peptidases. REP34 possesses a novel topology and substrate binding pocket that deviates from the canonical funnelin structure of carboxypeptidases, putatively resulting in a catalytic role for a conserved tyrosine and distinct S1' recognition site. Taken together, these results identify REP34 as an active carboxypeptidase, implicate the enzyme as a potential key F. tularensis effector protein, and may help elucidate a mechanistic understanding of F. tularensis infection of phagocytic cells. Structure and function of REP34 implicates carboxypeptidase activity in Francisella tularensis host-cell invasion.,Feld GK, El-Etr S, Corzett MH, Hunter MS, Belhocine K, Monack DM, Frank M, Segelke BW, Rasley A J Biol Chem. 2014 Sep 17. pii: jbc.M114.599381. PMID:25231992[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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