LcrV protein (V antigen) of Yersinia pestis (LcrV)

The LcrV protein (commonly known as V antigen) is a multifunctional virulence factor produced by Yersinia pestis, the causative agent of plague[1][3][4]. This soluble protein, consisting of 327 amino acids, regulates the translocation of cytotoxic effector proteins (Yops) from the bacterium into mammalian cells by acting as a key component of the type III secretion system (T3SS)[1][2][4]. LcrV functions by binding the inner-gate protein LcrG and modulating the T3SS machinery, enabling the targeted secretion of Yops and contributing to the full virulence of Y. pestis[2][4]. Apart from its role in secretion regulation, LcrV also possesses immunomodulatory activities, notably suppressing host immune responses by altering cytokine profiles. The protein contains distinct regions important for both immune protection and virulence, and antibodies directed against the central protective region of LcrV can confer immunity in animal models[3][4]. As such, LcrV is a validated target for both passive and active immunization strategies and is a principal candidate for plague subunit vaccines. A notable homolog of LcrV is the PcrV protein from Pseudomonas aeruginosa, sharing high sequence similarity at the C-terminus, which is critical for secretion activation[2][4]. Hypervariable regions in LcrV may influence vaccine protection across different Yersinia species[3]. No small-molecule drugs are approved to target LcrV, but therapeutic antibodies and vaccine constructs are in preclinical and clinical evaluation. The crystal structure of LcrV exhibits a novel fold and a coiled-coil motif and is essential for understanding its function as a virulence determinant and vaccine antigen[1].

Other names

V antigenLcrVlow-calcium response V antigen

Antibodies against LcrV neutralize virulence by blocking its function in T3SS, thereby interfering with the bacterium’s ability to inject effector proteins into host cells[3][4].