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TitleThe mechanism of the phage-encoded protein antibiotic from ΦX174.
Journal, issue, pagesScience, Vol. 381, Issue 6654, Page eadg9091, Year 2023
Publish dateJul 14, 2023
AuthorsAnna K Orta / Nadia Riera / Yancheng E Li / Shiho Tanaka / Hyun Gi Yun / Lada Klaic / William M Clemons /
PubMed AbstractThe historically important phage ΦX174 kills its host bacteria by encoding a 91-residue protein antibiotic called protein E. Using single-particle electron cryo-microscopy, we demonstrate that ...The historically important phage ΦX174 kills its host bacteria by encoding a 91-residue protein antibiotic called protein E. Using single-particle electron cryo-microscopy, we demonstrate that protein E bridges two bacterial proteins to form the transmembrane YES complex [MraY, protein E, sensitivity to lysis D (SlyD)]. Protein E inhibits peptidoglycan biosynthesis by obstructing the MraY active site leading to loss of lipid I production. We experimentally validate this result for two different viral species, providing a clear model for bacterial lysis and unifying previous experimental data. Additionally, we characterize the MraY structure-revealing features of this essential enzyme-and the structure of the chaperone SlyD bound to a protein. Our structures provide insights into the mechanism of phage-mediated lysis and for structure-based design of phage therapeutics.
External linksScience / PubMed:37440661
MethodsEM (single particle)
Resolution3.4 - 3.5 Å
Structure data

29641

8g01

EMDB-29641, PDB-8g01:
YES Complex - E. coli MraY, Protein E ID21, E. coli SlyD
Method: EM (single particle) / Resolution: 3.4 Å

29642

8g02

EMDB-29642: YES Complex - E. coli MraY, Protein E ID21, E. coli SlyD
PDB-8g02: YES Complex - E. coli MraY, Protein E PhiX174, E. coli SlyD
Method: EM (single particle) / Resolution: 3.5 Å

Source
  • escherichia phage id21 (virus)
  • escherichia coli k-12 (bacteria)
  • escherichia phage phix174 (virus)
KeywordsTRANSFERASE/ISOMERASE / inhibitor / antibiotic / chaperone / membrane / bacteriophage / TRANSFERASE-ISOMERASE complex

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