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Published September 2012 | Accepted Version + Supplemental Material
Journal Article Open

Minimal requirements for inhibition of MraY by lysis protein E from bacteriophage ΦX174


The DNA phage ΦX174 encodes the integral membrane protein E whose expression leads to host cell lysis by inhibition of the peptidoglycan synthesis enzyme MraY. Here we use mutagenesis to characterize the molecular details of the E lysis mechanism. We find that a minimal 18-residue region with the modified wild-type sequences of the conserved transmembrane helix of E is sufficient to lyse host cells and that specific residues within and at the boundaries of this helix are important for activity. This suggests that positioning of the helix in the membrane is critical for interactions with MraY. We further characterize the interaction site of the transmembrane helix with MraY demonstrating E forms a stable complex with MraY. Triggering cell lysis by peptidoglycan synthesis inhibition is a traditional route for antimicrobial strategies. Understanding the mechanism of bacterial cell lysis by E will provide insights into new antimicrobial strategies using re-engineered E peptides.

Additional Information

© 2012 Blackwell Publishing Ltd. Accepted 22 June, 2012. First published online 13 July 2012. We are grateful to Jaeyoon Chung and Nadia Iqbal for help in generating the mutant constructs. We thank R. Young and T.O. Yeates for critical reading of the manuscript. We thank members of the laboratory for support and useful discussion. The slyD knockout strain and the anti-MraY antibody were kindly provided by Ry Young, Texas A&M University. This work is supported by a Jane Coffin Childs Memorial Fund fellowship to S.T. and a Searle Scholar fellowship, a Burroughs-Wellcome Fund Career Award and a NIH Pioneer Award (Grant 1DP1OD008304-01) to W.M.C.

Attached Files

Accepted Version - nihms391096.pdf

Supplemental Material - MMI_8153_sm_FS1-4-TS1-2.pdf


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August 19, 2023
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