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Crystal structure of Francisella tularensis REP34 (Rapid Encystment Phenotype Protein 34 KDa)Crystal structure of Francisella tularensis REP34 (Rapid Encystment Phenotype Protein 34 KDa)
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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