Structure and Function of Hoc—A Novel Environment Sensing Device Encoded by T4 and Other Bacteriophages
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-bindin...
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| Format: | Article |
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MDPI AG
2023-07-01
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| Series: | Viruses |
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| Online Access: | https://www.mdpi.com/1999-4915/15/7/1517 |
| _version_ | 1797587242838917120 |
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| author | Andrei Fokine Mohammad Zahidul Islam Qianglin Fang Zhenguo Chen Lei Sun Venigalla B. Rao |
| author_facet | Andrei Fokine Mohammad Zahidul Islam Qianglin Fang Zhenguo Chen Lei Sun Venigalla B. Rao |
| author_sort | Andrei Fokine |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-03-11T00:34:21Z |
| format | Article |
| id | doaj.art-8fdf11febe3747618ae1031ef06bf1e5 |
| institution | Directory Open Access Journal |
| issn | 1999-4915 |
| language | English |
| last_indexed | 2024-03-11T00:34:21Z |
| publishDate | 2023-07-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Viruses |
| spelling | doaj.art-8fdf11febe3747618ae1031ef06bf1e52023-11-18T21:44:49ZengMDPI AGViruses1999-49152023-07-01157151710.3390/v15071517Structure and Function of Hoc—A Novel Environment Sensing Device Encoded by T4 and Other BacteriophagesAndrei Fokine0Mohammad Zahidul Islam1Qianglin Fang2Zhenguo Chen3Lei Sun4Venigalla B. Rao5Department of Biological Sciences, Purdue University, West Lafayette, IN 47907, USABacteriophage Medical Research Center, Department of Biology, The Catholic University of America, Washington, DC 20064, USADepartment of Biological Sciences, Purdue University, West Lafayette, IN 47907, USADepartment of Biological Sciences, Purdue University, West Lafayette, IN 47907, USADepartment of Biological Sciences, Purdue University, West Lafayette, IN 47907, USABacteriophage Medical Research Center, Department of Biology, The Catholic University of America, Washington, DC 20064, USABacteriophage 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.https://www.mdpi.com/1999-4915/15/7/1517bacteriophage T4phage head structurehighly immunogenic outer capsid protein Hoccapsid decoration proteinphage displayantigen display |
| spellingShingle | Andrei Fokine Mohammad Zahidul Islam Qianglin Fang Zhenguo Chen Lei Sun Venigalla B. Rao Structure and Function of Hoc—A Novel Environment Sensing Device Encoded by T4 and Other Bacteriophages Viruses bacteriophage T4 phage head structure highly immunogenic outer capsid protein Hoc capsid decoration protein phage display antigen display |
| title | Structure and Function of Hoc—A Novel Environment Sensing Device Encoded by T4 and Other Bacteriophages |
| title_full | Structure and Function of Hoc—A Novel Environment Sensing Device Encoded by T4 and Other Bacteriophages |
| title_fullStr | Structure and Function of Hoc—A Novel Environment Sensing Device Encoded by T4 and Other Bacteriophages |
| title_full_unstemmed | Structure and Function of Hoc—A Novel Environment Sensing Device Encoded by T4 and Other Bacteriophages |
| title_short | Structure and Function of Hoc—A Novel Environment Sensing Device Encoded by T4 and Other Bacteriophages |
| title_sort | structure and function of hoc a novel environment sensing device encoded by t4 and other bacteriophages |
| topic | bacteriophage T4 phage head structure highly immunogenic outer capsid protein Hoc capsid decoration protein phage display antigen display |
| url | https://www.mdpi.com/1999-4915/15/7/1517 |
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