Viral Ejection Proteins: Mosaically Conserved, Conformational Gymnasts.

Nicholas Swanson,Gino Cingolani,Chun-Feng Hou

doi:10.3390/microorganisms10030504

Nicholas Swanson, Gino Cingolani + Show 1 more

Open Access

https://doi.org/10.3390/microorganisms10030504

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Abstract

Bacterial viruses (or bacteriophages) have developed formidable ways to deliver their genetic information inside bacteria, overcoming the complexity of the bacterial-cell envelope. In short-tailed phages of the Podoviridae superfamily, genome ejection is mediated by a set of mysterious internal virion proteins, also called ejection or pilot proteins, which are required for infectivity. The ejection proteins are challenging to study due to their plastic structures and transient assembly and have remained less characterized than classical components such as the phage coat protein or terminase subunit. However, a spate of recent cryo-EM structures has elucidated key features underscoring these proteins’ assembly and conformational gymnastics that accompany their expulsion from the virion head through the portal protein channel into the host. In this review, we will use a phage-T7-centric approach to critically review the status of the literature on ejection proteins, decipher the conformational changes of T7 ejection proteins in the pre- and post-ejection conformation, and predict the conservation of these proteins in other Podoviridae. The challenge is to relate the structure of the ejection proteins to the mechanisms of genome ejection, which are exceedingly complex and use the host’s machinery.

Highlights

Bacteriophages are the most diverse and abundant biological entities on the planet [1]
Phage-tail morphology has inspired a common classification of tailed phages, which are usually divided into three broad morphotypes: Myoviridae, characterized by long, contractile tails such as the popular spiderlike phage T4; Siphoviridae, which have long, non-contractile and floppy tails such as phage lambda; and Podoviridae, which contain short, non-contractile tails such as T7 and P22 [6,7]
Interactions with receptors often trigger drastic conformational changes resulting in phage genome ejection [9,10,11]

Summary

Introduction

Bacteriophages (phages/viruses that infect bacteria) are the most diverse and abundant biological entities on the planet [1]. The periplasmic space of Gram-negative bacteria is a harsh oxidizing environment that contains a peptidoglycan cell wall and houses several host enzymes that are capable of degrading phage DNA [23,24,25,26] To overcome this physical barrier, Podoviridae phages carry their own genome-delivery conduit assembled from a set of internal virion proteins, named ejection or pilot proteins, that are required for infectivity [19]. If the created phage machinery constitutively opens pores, the host membrane potential and cellular integrity would be disrupted, leading to premature lysis prior to viral replication, sometimes called “lysis from without” [40,41,42,43] Perhaps due to these challenges, ejection proteins have remained generally understudied compared to the classical structural components of a phage capsid. We explore the conformational gymnastics of T7 ejection proteins and their conservation across Podoviridae

The T7 DNA Ejectosome

Conformational Gymnastics of T7 Ejection Proteins

Conservation of Ejection Proteins

Models for Ejection-Protein Assembly into a DNA Ejectosome

Findings

Conclusive Remarks