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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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Autores principales: Fokine, Andrei, Islam, Mohammad Zahidul, Fang, Qianglin, Chen, Zhenguo, Sun, Lei, Rao, Venigalla B.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10385173/
https://www.ncbi.nlm.nih.gov/pubmed/37515203
http://dx.doi.org/10.3390/v15071517
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author Fokine, Andrei
Islam, Mohammad Zahidul
Fang, Qianglin
Chen, Zhenguo
Sun, Lei
Rao, Venigalla B.
author_facet Fokine, Andrei
Islam, Mohammad Zahidul
Fang, Qianglin
Chen, Zhenguo
Sun, Lei
Rao, Venigalla B.
author_sort Fokine, Andrei
collection PubMed
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.
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spelling pubmed-103851732023-07-30 Structure and Function of Hoc—A Novel Environment Sensing Device Encoded by T4 and Other Bacteriophages Fokine, Andrei Islam, Mohammad Zahidul Fang, Qianglin Chen, Zhenguo Sun, Lei Rao, Venigalla B. Viruses Article 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. MDPI 2023-07-07 /pmc/articles/PMC10385173/ /pubmed/37515203 http://dx.doi.org/10.3390/v15071517 Text en © 2023 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Fokine, Andrei
Islam, Mohammad Zahidul
Fang, Qianglin
Chen, Zhenguo
Sun, Lei
Rao, Venigalla B.
Structure and Function of Hoc—A Novel Environment Sensing Device Encoded by T4 and Other Bacteriophages
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 Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10385173/
https://www.ncbi.nlm.nih.gov/pubmed/37515203
http://dx.doi.org/10.3390/v15071517
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