Regulated Intramembrane Proteolysis of the Virulence Activator TCPP in Vibrio cholerae.

Vibrio cholerae;TcpP;regulated intramembrane proteolysis;TcpH;Tsp;YaeL;Microbiology and Immunology;Science;Microbiology and Immunology

Teoh, Wei PingSandkvist, Maria B. ;

University of Michigan

关键词: Vibrio cholerae;    TcpP;    regulated intramembrane proteolysis;    TcpH;    Tsp;    YaeL;    Microbiology and Immunology;    Science;    Microbiology and Immunology;   

Others  :  https://deepblue.lib.umich.edu/bitstream/handle/2027.42/113400/teoh_1.pdf?sequence=1&isAllowed=y

瑞士|英语

来源: The Illinois Digital Environment for Access to Learning and Scholarship

【 摘 要 】

In Vibrio cholerae, direct activation of genes that encode cholera toxin (CT) and toxin-coregulated pilus (TCP) requires the ToxT transcription activator, whose expression is regulated by a complex of membrane regulatory proteins including ToxR and TcpP. TcpP, with a cytoplasmic domain similar to that found in OmpR and a periplasmic domain that may respond to specific environmental signals, is degraded in a two-step proteolytic pathway known as regulated intramembrane proteolysis (RIP), which eliminates the expression of CT and TCP. Under specific conditions, degradation is inhibited by another membrane-bound periplasmic protein, TcpH. I applied forward and reverse genetic approaches to determine the site-1 protease of TcpP. Through these analyses, I found that a C-terminal protease called Tsp catalyzes TcpP degradation to a truncated yet still active species that we termed TcpP*, which is the substrate for the previously identified site-2 protease, YaeL. Moreover, my results indicate a role of TcpH in protecting full-length TcpP from spurious degradation by YaeL. I investigate the possibility of RIP regulating steady-state levels of TcpH and present evidence that TcpP confers stability to TcpH. Furthermore, in vivo studies in infant mice suggest that YaeL, but not Tsp, is required for intestinal colonization. These results expand our knowledge about RIP and the unorthodox mechanism of gene activation by membrane-bound transcription factors.