Structure of AcrH–AopB Chaperone-Translocator Complex Reveals a Role for Membrane Hairpins in Type III Secretion System Translocon Assembly

• Published in: Structure (London) Vol. 23; no. 11; pp. 2022 - 2031
• Main Authors: Nguyen, Van Sang, Jobichen, Chacko, Tan, Kang Wei, Tan, Yih Wan, Chan, Siew Leong, Ramesh, Karthik, Yuan, Yongming, Hong, Yunhan, Seetharaman, Jayaraman, Leung, Ka Yin, Sivaraman, J., Mok, Yu Keung
• Format: Journal Article
• Language: English
• Published: United States Elsevier Ltd 03-11-2015
• Subjects: Aeromonas hydrophila - chemistry; Amino Acid Sequence; Binding Sites; Molecular Chaperones - chemistry; Molecular Chaperones - metabolism; Molecular Dynamics Simulation; Molecular Sequence Data; Protein Binding; Type III Secretion Systems - chemistry; Type III Secretion Systems - metabolism
• ISSN: 0969-2126; 1878-4186
• DOI: 10.1016/j.str.2015.08.014

Type III secretion systems (T3SSs) are adopted by pathogenic bacteria for the transport of effector proteins into host cells through the translocon pore composed of major and minor translocator proteins. Both translocators require a dedicated chaperone for solubility. Despite tremendous efforts in the past, structural information regarding the chaperone-translocator complex and the topology of the translocon pore have remained elusive. Here, we report the crystal structure of the major translocator, AopB, from Aeromonas hydrophila AH-1 in complex with its chaperone, AcrH. Overall, the structure revealed unique interactions between the various interfaces of AopB and AcrH, with the N-terminal “molecular anchor” of AopB crossing into the “N-terminal arm” of AcrH. AopB adopts a novel fold, and its transmembrane regions form two pairs of helical hairpins. From these structural studies and associated cellular assays, we deduced the topology of the assembled T3SS translocon; both termini remain extracellular after membrane insertion.
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•N-terminal arm of chaperone crosses over into translocator for essential interaction•Coiled-coil helices are bent and wrap around the chaperone and transmembrane region•Transmembrane regions of translocator form 2 hairpins in the presence of the chaperone•Both N and C termini of translocator remain extracellular after membrane insertion
Nguyen et al. present the structure of the chaperone-major translocator complex in the bacterial type III secretion system, showing that transmembrane regions of the translocator form two hairpins. Both the N- and C-terminal coiled-coil regions remain extracellular after membrane insertion.