bid-f1 and bid-f2 domains of bartonella henselae effector protein bepf trigger together with bepc the formation of invasome structuresbid-f1和bid-f2域的巴尔通氏体属henselae效应蛋白bepf引发一起bepc invasome结构的形成.pdfVIP

BID-F1 and BID-F2 Domains of Bartonella henselae Effector Protein BepF Trigger Together with BepC the Formation of Invasome Structures 1 1,2 1 Matthias C. Truttmann , Patrick Guye , Christoph Dehio * 1 Focal Area Infection Biology, Biozentrum of the University of Basel, Basel, Switzerland, 2 Department of Biological Engineering, Massachusetts Institute of Technology (MIT), Cambridge, Massachusetts, United States of America Abstract The gram-negative, zoonotic pathogen Bartonella henselae (Bhe) translocates seven distinct Bartonella effector proteins (Beps) via the VirB/VirD4 type IV secretion system (T4SS) into human cells, thereby interfering with host cell signaling [1,2]. In particular, the effector protein BepG alone or the combination of effector proteins BepC and BepF trigger massive F-actin rearrangements that lead to the establishment of invasome structures eventually resulting in the internalization of entire Bhe aggregates [2,3]. In this report, we investigate the molecular function of the effector protein BepF in the eukaryotic host cell. We show that the N-terminal [E/T]PLYAT tyrosine phosphorylation motifs of BepF get phosphorylated upon translocation but do not contribute to invasome-mediated Bhe uptake. In contrast, we found that two of the three BID domains of BepF are capable to trigger invasome formation together with BepC, while a mutation of the WxxxE motif of the BID-F1 domain inhibited its ability to contribute to the formation of invasome structures. Next, we show that BepF function during invasome formation can be replaced by the over-expression of constitutive-active Rho GTPases Rac1 or Cdc42. Finally we demonstrate that BID-F1 and BID-F2 domains promote the formation of f