YopH

YopH is a virulence factor protein tyrosine phosphatase used by pathogenic Yersinia species, including Yersinia pestis, Y. enterocolitica, and Y. pseudotuberculosis. It is delivered directly into host cells via the bacteria’s type III secretion system, where it functions to counter host immune responses by removing phosphate groups from tyrosine residues on specific host signaling proteins.

The protein comprises an N-terminal region that facilitates secretion and translocation into host cells, and a C-terminal catalytic protein tyrosine phosphatase (PTP) domain. The active site contains a catalytic cysteine within a conserved HCX5R motif, a hallmark of classical PTPs. In host cells, YopH localizes to sites of focal adhesion and cytoskeletal assembly.

Once inside the cell, YopH dephosphorylates a range of substrates involved in signaling pathways that regulate cytoskeletal dynamics and endocytosis. Notable targets include focal adhesion components such as p130Cas and paxillin, as well as other signaling proteins like FAK. By dephosphorylating these proteins, YopH disrupts integrin signaling and actin remodeling, thereby inhibiting phagocytosis and the intracellular killing of bacteria by macrophages and neutrophils.

YopH is a major determinant of Yersinia virulence; deletion of yopH often results in attenuated virulence in animal models. Expression and secretion are coordinated with the type III secretion system and environmental cues, enabling rapid modulation of host-pathogen interactions during infection.

In research, YopH is a well-studied example of a bacterial effector PTP, contributing to understanding of phosphotyrosine signaling and host immune evasion.