The Phage T4 Antiholin RI Has a Cleavable Signal Peptide, Not a SAR Domain

authored by
Denise Mehner-Breitfeld, Jan Michel Frederik Schwarzkopf, Ry Young, Kiran Kondabagil, Thomas Brüser

Holin/endolysin-mediated lysis of phage T4 of Escherichia coli is tightly regulated by the antiholins RI and RIII. While regulation by the cytoplasmic RIII plays a minor role, the periplasmic antiholin RI binds tightly to the holin T and is believed to directly sense periplasmic phage DNA from superinfections as a trigger for the inhibition of lysis. RI has been reported to contain a non-cleavable signal peptide that anchors the protein to the membrane. Lysis is believed to be induced at some stage by a membrane depolarization that causes a release of RI into the periplasm without cleavage of the signal anchor. For the current model of phage lysis induction, it is thus a fundamental assumption that the N-terminal trans-membrane domain (TMD) of RI is such a signal anchor release (SAR) domain. Here we show that, in contrast to previous reports, this domain of RI is a cleavable signal peptide. RI is processed and released into the periplasm as a mature protein, and inactivation of its signal peptidase cleavage site blocks processing and membrane release. The signal peptide of RI can also mediate the normal translocation of a well-characterized Sec substrate, PhoA, into the periplasm. This simplifies the current view of phage lysis regulation and suggests a fundamentally different interpretation of the recently published structure of the soluble domains of the RI–T complex.

Institute of Microbiology
External Organisation(s)
Texas A and M University
Indian Institute of Technology Bombay (IITB)
Frontiers in Microbiology
No. of pages
Publication date
Publication status
Peer reviewed
ASJC Scopus subject areas
Microbiology (medical), Microbiology
Research Area (based on ÖFOS 2012)
Electronic version(s) (Access: Open)