MODULATION OF THE ACTIN CYTOSKELETON THROUGH PHOSPHORYLATION OF ACTIN REGULATORS BY YERSINIA YOPO

Abstract

YERSINIA MODULATE AND EVADE HOST IMMUNE SYSTEMS THROUGH INJECTION OF YERSINIA OUTER PROTEINS (YOPS) INTO PHAGOCYTIC CELLS. YOPO, ONE OF THE YOPS, IMPAIRS PHAGOCYTOSIS THROUGH ACTIN FILAMENT DISRUPTION USING MONOMERIC ACTIN AS A BAIT TO RECRUIT AND PHOSPHORYLATE HOST ACTIN POLYMERIZATION REGULATING PROTEINS. HERE, WE REPORT THE MGADP STRUCTURE OF YERSINIA ENTEROCOLITICA YOPO, IN COMPLEX WITH ACTIN, WHICH REVEALS THE ACTIVE SITE ARCHITECTURE OF THE KINASE DOMAIN. YOPO PHOSPHORYLATION SITES ON GELSOLIN, MDIA1, VASP, EVL AND WASP WERE IDENTIFIED BY MASS SPECTROMETRY. PHOSPHORYLATION EVENTS ON VASP AND MDIA1 ATTENUATE THEIR ABILITIES TO ACCELERATE IN VITRO ACTIN POLYMERIZATION. IN CONTRAST, PHOSPHORYLATION OF WASP BY YOPO HAS NO OBSERVABLE EFFECT ON ARP2/3 ACTIVATION. YOPO PHOSPHORYLATES GELSOLIN IN THE LINKER REGION BETWEEN G3-G4 TO GIVE RISE TO CALCIUM-INDEPENDENT ACTIVITY. THESE FINDINGS INDICATE THAT PHOSPHORYLATION OF ACTIN POLYMERIZATION REGULATORS BY YOPO LEADS TO ALTERED ACTIVITIES,