Structural remodeling of bacteriophage T4 and host membranes during infection initiation

Proc Natl Acad Sci U S A. 2015 Sep 1;112(35):E4919-28. doi: 10.1073/pnas.1501064112. Epub 2015 Aug 17.


The first stages of productive bacteriophage infections of bacterial host cells require efficient adsorption to the cell surface followed by ejection of phage DNA into the host cytoplasm. To achieve this goal, a phage virion must undergo significant structural remodeling. For phage T4, the most obvious change is the contraction of its tail. Here, we use skinny E. coli minicells as a host, along with cryo-electron tomography and mutant phage virions, to visualize key structural intermediates during initiation of T4 infection. We show for the first time that most long tail fibers are folded back against the tail sheath until irreversible adsorption, a feature compatible with the virion randomly walking across the cell surface to find an optimal site for infection. Our data confirm that tail contraction is triggered by structural changes in the baseplate, as intermediates were found with remodeled baseplates and extended tails. After contraction, the tail tube penetrates the host cell periplasm, pausing while it degrades the peptidoglycan layer. Penetration into the host cytoplasm is accompanied by a dramatic local outward curvature of the cytoplasmic membrane as it fuses with the phage tail tip. The baseplate hub protein gp27 and/or the ejected tape measure protein gp29 likely form the transmembrane channel for viral DNA passage into the cell cytoplasm. Building on the wealth of prior biochemical and structural information, this work provides new molecular insights into the mechanistic pathway of T4 phage infection.

Keywords: cryo-ET; infected cell; membrane curvature; phage T4; structure.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Bacteriophage T4 / genetics
  • Bacteriophage T4 / physiology*
  • Cell Membrane / virology
  • Cryoelectron Microscopy
  • Genes, Viral
  • Host-Pathogen Interactions*
  • Viral Tail Proteins / chemistry
  • Virion


  • Viral Tail Proteins