Common themes in the design and function of bacterial effectors

Abstract

Central to the biology of many pathogenic bacteria are a number of specialized machines, known as type III, type IV, or type VI protein secretion systems. These machines have specifically evolved to deliver bacterial effector proteins into host cells with the capacity to modulate a variety of cellular functions. The identification of the biochemical activities of many effector proteins, coupled with a better understanding of their potential contribution to pathogenesis, has revealed common themes in the evolutionary design and function of these remarkable bacterial proteins.

Figure 1. Structural mimicry in type III secreted effector proteins

A. S. Typhimurium SopE mimics Rho-family GEFs. The conformational changes induced on the G-domain of Cdc42 by SopE (shown in green) are similar to those induced by mammalian exchange factor Tiam1 on Rac1 (shown in grey). The P loop, switch I/II regions are shown for the individual molecules. Relevant regions of SopE and Tiam1 are shown in red and blue, respectively. The view shows the similar location of the catalytic loop from SopE and the important Lys1195 from Tiam [taken from (Buchwald et al., 2002)]. B. S. Typhimurium SptP mimics Rho-family GAPs. The active sites of three transition-state complexes between small GTPases (Rac1, Cdc42, and Ras) and their cognate GAPs (SptP, Cdc42 GAP, and Ras GAP) depicting the nucleotide and catalytic arginine present in all known GAPs are shown. This image illustrates that despite using a similar chemistry to the host factors, SptP (in blue) presents the arginine from a completely different protein architecture. AlFX, aluminium fluoride [taken from (Stebbins and Galán, 2001)]. C. Effector proteins mimic three different types of E3 ligases. Shown are the E3 ligase domains of S. Typhimurium SspH2, showing the NEL domain, S. Typhimurium SopA, a HECT family of cysteine dependent E3 ubiquitin ligases from Salmonella, and AvrPtoB, a RING finger/U-box protein. The catalytic cysteine residues are shown in a space-filling format colored blue [taken from (Quezada et al., 2009)].