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Regulated intramembrane proteolysis of the virulence activator TcpP in V ibrio cholerae is initiated by the tail‐specific protease ( T sp)
Author(s) -
Teoh Wei Ping,
Matson Jyl S.,
DiRita Victor J.
Publication year - 2015
Publication title -
molecular microbiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.857
H-Index - 247
eISSN - 1365-2958
pISSN - 0950-382X
DOI - 10.1111/mmi.13069
Subject(s) - biology , vibrio cholerae , periplasmic space , cholera toxin , proteolysis , protease , microbiology and biotechnology , activator (genetics) , biochemistry , gene , escherichia coli , enzyme , genetics , bacteria
Summary V ibrio cholerae uses a multiprotein transcriptional regulatory cascade to control expression of virulence factors cholera toxin and toxin‐co‐regulated pilus. Two proteins in this cascade are ToxR and TcpP – unusual membrane‐localized transcription factors with relatively undefined periplasmic domains and transcription activator cytoplasmic domains. TcpP and ToxR function with each other and two other membrane‐localized proteins, TcpH and ToxS , to activate transcription of toxT , encoding the direct activator of toxin and pilus genes. Under some conditions, TcpP is degraded in a two‐step proteolytic pathway known as regulated intramembrane proteolysis ( RIP ), thereby inactivating the cascade. The second step in this proteolytic pathway involves the zinc metalloprotease YaeL ; V . cholerae cells lacking YaeL accumulate a truncated yet active form of TcpP termed TcpP *. We hypothesized that a protease acting prior to YaeL degrades TcpP to TcpP *, which is the substrate of YaeL . In this study, we demonstrate that a C ‐terminal protease called T sp degrades TcpP to form TcpP *, which is then acted upon by YaeL . We present evidence that TcpH and T sp serve to protect full‐length TcpP from spurious proteolysis by YaeL . Cleavage by T sp occurs in the periplasmic domain of TcpP and requires residues TcpPA 172 and TcpPI 174 for wild‐type activity.