Download MendeleyStructure and Function of Hoc-A Novel Environment Sensing Device Encoded by T4 and Other Bacteriophages.
Fokine, A., Islam, M.Z., Fang, Q., Chen, Z., Sun, L., Rao, V.B.(2023) Viruses 15
- PubMed: 37515203
- DOI: https://doi.org/10.3390/v15071517
- Primary Citation of Related Structures:
8T1X, 8T9R - PubMed Abstract:
Bacteriophage T4 is decorated with 155 180 Å-long fibers of the highly antigenic outer capsid protein (Hoc). In this study, we describe a near-atomic structural model of Hoc by combining cryo-electron microscopy and AlphaFold structure predictions. It consists of a conserved C-terminal capsid-binding domain attached to a string of three variable immunoglobulin (Ig)-like domains, an architecture well-preserved in hundreds of Hoc molecules found in phage genomes. Each T4-Hoc fiber attaches randomly to the center of gp23* hexameric capsomers in one of the six possible orientations, though at the vertex-proximal hexamers that deviate from 6-fold symmetry, Hoc binds in two preferred orientations related by 180° rotation. Remarkably, each Hoc fiber binds to all six subunits of the capsomer, though the interactions are greatest with three of the subunits, resulting in the off-centered attachment of the C-domain. Biochemical analyses suggest that the acidic Hoc fiber (pI, ~4-5) allows for the clustering of virions in acidic pH and dispersion in neutral/alkaline pH. Hoc appears to have evolved as a sensing device that allows the phage to navigate its movements through reversible clustering-dispersion transitions so that it reaches its destination, the host bacterium, and persists in various ecological niches such as the human/mammalian gut.
Organizational Affiliation:
Department of Biological Sciences, Purdue University, West Lafayette, IN 47907, USA.
