Expanded Roles for Multicargo and Class 1B Effector Chaperones in Type III Secretion

Abstract

bBacterial type III secretion systems (T3SS) are complex protein assemblies that mediate the secretion of protein substrates outside the cell. Type III secretion chaperones (T3SC) are always found associated with T3SS, and they serve in multiple roles to ensure that protein substrates are efficiently targeted for secretion. Bacterial pathogens with T3SS express T3SC proteins that bind effectors, a process important for effector protein delivery into eukaryotic cells during infection. In this minireview, we focus on multicargo and class 1B T3SC that associate with effectors within significant pathogens of animals and plants. As a primary role, multicargo and class 1B T3SC form homodimers and specifically bind different effectors within the cytoplasm, maintaining the effectors in a secretion-competent state. This role makes T3SC initial and central contributors to effector-mediated pathogenesis. Recent findings have greatly expanded our understanding of cellular events linked to multicargo T3SC function. New binding interactions with T3SS components have been reported in different systems, thereby implicating multicargo T3SC in critical roles beyond effector binding. Three notable interactions with the YscN, YscV, and YscQ family members are well represented in the literature. Similar T3SC interactions are reported in the putative related flagellar T3SS, suggesting that secretion mechanisms may be more similar than previously thought. The evidence implicates multicargo and class 1B T3SC in effector binding and stabilization, in addition to T3SS recruitment and docking events.

Identification of Novel Type III Secretion Chaperone-Substrate Complexes of Chlamydia trachomatis

“…We do not know the exact reason why expression of Slc1 or CT584 in ΔHOPEMT affected secretion of YopB, YopD, YopN, and LcrV, but not of YopE-Myc or of YscP. However, T3S chaperones need to interact with the injectisome to release their substrates before secretion [2], [56], and therefore Slc1 and CT584 may interact with components of the Yersinia injectisome to help T3S of their substrates (Tarp, CT694, CT695, and CT082). Considering that Slc1 and CT584 did not evolve in Yersinia , their possible interaction with components of the Y. enterocolitica injectisome may also hamper the normal functioning of this T3SS.…”

“…Effector T3S chaperones (class I chaperones) normally bind to the N-terminal region of their substrates and are distinguished according to whether they have one (class IA) or several substrates (class IB) [2], [10]. Slc1 is at least the chaperone of two known chlamydial effectors (Tarp and CT694), and of one chlamydial T3S substrate (CT695), and binds to their N-terminal regions.…”

Role of EscP (Orf16) in Injectisome Biogenesis and Regulation of Type III Protein Secretion in Enteropathogenic Escherichia coli

“…2), which suggests that EscP is needed for regulation of effector secretion. In EPEC, the LEE-encoded type III chaperone CesT interacts with at least eight effectors (9,13,99,100,102) and with the type III ATPase EscN, serving to target effectors to the export apparatus (37). In order to determine whether EscP interacts with this chaperone, we performed copurification assays by MBP affinity chromatography.…”

Bacterial Type III Secretion Systems: Specialized Nanomachines for Protein Delivery into Target Cells

“…T3SS chaperones exhibit limited primary amino-acid sequence similarity to one another although they share structural similarity as well as some physical properties, such a small size and an acidic pI (135). Based on their tertiary structure and specificity of binding, these chaperones have been classified in two general groups referred to as class I and class II (33; 116; 137). An additional distinction is usually made among class I chaperones between those that bind a single protein (unicargo) vs those that bind several (multicargo).…”