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
Abstract: 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.
Organisation(s): Institute of Microbiology
External Organisation(s): Texas A and M University
Indian Institute of Technology Bombay (IITB)
Type: Article
Journal: Frontiers in Microbiology
Volume: 12
No. of pages: 8
ISSN: 1664-302X
Publication date: 11.08.2021
Publication status: Published
Peer reviewed: Yes
ASJC Scopus subject areas: Microbiology (medical), Microbiology
Research Area (based on ÖFOS 2012): Biochemistry
Electronic version(s): https://doi.org/10.3389/fmicb.2021.712460 (Access: Open)