bacteriophage Qbeta

The genome of Qβ is approximately 4,217 nucleotides, depending on the source which sequenced the virus. Qβ has been isolated all over the world, multiple times, with various subspecies that code for nearly identical proteins but can have very different nucleotide sequences.{{citation needed|date=October 2022}}

The genome has three open reading frames that encode four proteins: the maturation/lysis protein A2; the coat protein; a readthrough of a leaky stop codon in the coat protein, called A1; and the β-subunit of an RNA-dependent RNA-polymerase (RdRp) termed the replicase. The genome is highly structured, regulating gene expression and protecting itself from host RNases.

There are approximately 178 copies of the coat protein and/or A1 in the capsid.{{citation needed|date=October 2022}}

The RNA-dependent RNA polymerase that replicates both the positive and negative RNA strands is a complex of four proteins: the catalytic beta subunit (replicase, {{UniProt|P14647}}) is encoded by the phage, while the other three subunits are encoded by the bacterial genome: alpha subunit (ribosomal protein S1), gamma subunit (EF-Tu), and delta subunit (EF-Ts).{{cite book|url=https://archive.org/details/bacteriophagesed00abed|title=The Bacteriophages|vauthors=van Duin J, Tsareva N|publisher=Oxford University Press|year=2006|isbn=978-0195148503|veditors=Calendar RL|edition=Second|pages=[https://archive.org/details/bacteriophagesed00abed/page/n189 175]–196|chapter=Single-stranded RNA phages. Chapter 15|url-access=limited}}

The structure of the Qbeta RNA replicase has been solved ({{PDB|3AGP|3AGQ}}). The two EF proteins serve as a chaperone for both the replicase and the RNA product.{{cite journal|vauthors=Takeshita D, Tomita K|date=September 2010|title=Assembly of Q{beta} viral RNA polymerase with host translational elongation factors EF-Tu and -Ts|journal=Proceedings of the National Academy of Sciences of the United States of America|volume=107|issue=36|pages=15733–8|doi=10.1073/pnas.1006559107|pmc=2936634|pmid=20798060|doi-access=free}} In fact, pure Qbeta polymerase is not soluble enough to be produced in large quantities, and a fusion protein constructed from the replicase and the two EF subunits is usually used instead. The fusion can function independently of ribosomal protein S1.{{cite journal|vauthors=Kita H, Cho J, Matsuura T, Nakaishi T, Taniguchi I, Ichikawa T, Shima Y, Urabe I, Yomo T|date=May 2006|title=Functional Qbeta replicase genetically fusing essential subunits EF-Ts and EF-Tu with beta-subunit|journal=Journal of Bioscience and Bioengineering|volume=101|issue=5|pages=421–6|doi=10.1263/jbb.101.421|pmid=16781472}}

File:1-s2.0-S0022283615006762-gr1-C.jpg

All positive-strand RNA phages encode a maturation protein, whose function is to bind the host pilus and the viral RNA.{{cite book|vauthors=Rūmnieks J, Tārs K|chapter=Protein-RNA Interactions in the Single-Stranded RNA Bacteriophages |series=Subcellular Biochemistry |date=2018|title=Virus Protein and Nucleoprotein Complexes|publisher=Springer Singapore|volume=88|pages=281–303|doi=10.1007/978-981-10-8456-0_13|isbn=9789811084553|pmid=29900502|veditors=Harris RJ, Bhella D}} The maturation protein is named thus, as amber mutants in the maturation protein are unable to infect their host, or are 'immature.' For the related +ssRNA bacteriophage MS2, the maturation protein was shown to be taken up by the host along with the viral RNA and the maturation protein was subsequently cleaved.{{cite journal|vauthors=Paranchych W, Ainsworth SK, Dick AJ, Krahn PM|date=September 1971|title=Stages in phage R17 infection. V. Phage eclipse and the role of F pili|journal=Virology|volume=45|issue=3|pages=615–28|doi=10.1016/0042-6822(71)90176-0|pmid=4108185}}

In bacteriophage MS2, the maturation protein is called the A protein, as it belongs to the first open reading frame in the viral RNA. In Qβ the A protein was initially thought to be A1, as it is more abundant within the virion and is also required for infection.{{cite journal|vauthors=Moore CH, Farron F, Bohnert D, Weissmann C|date=September 1971|title=Possible origin of a minor virus specific protein (A1) in Q-beta particles|journal=Nature|volume=234|issue=50|pages=204–6|doi=10.1038/newbio234204a0|pmid=5288806}} However, once the sequence of Qβ was determined, A1 was revealed to be a readthrough of the leaky stop codon.{{citation needed|date=October 2022}}

A2 is the maturation protein for Qβ and has an additional role of being the lysis protein.{{cite journal|vauthors=Winter RB, Gold L|date=July 1983|title=Overproduction of bacteriophage Q beta maturation (A2) protein leads to cell lysis|journal=Cell|volume=33|issue=3|pages=877–85|doi=10.1016/0092-8674(83)90030-2|pmid=6871998|s2cid=54345352}}

The mechanism of lysis is similar to that of penicillin; A2 inhibits the formation of peptidoglycan by binding to MurA, which catalyzes the first enzymatically committed step in cell wall biosynthesis.{{cite journal|vauthors=Cui Z, Gorzelnik KV, Chang JY, Langlais C, Jakana J, Young R, Zhang J|date=October 2017|title=Structures of Qβ virions, virus-like particles, and the Qβ-MurA complex reveal internal coat proteins and the mechanism of host lysis|journal=Proceedings of the National Academy of Sciences of the United States of America|volume=114|issue=44|pages=11697–11702|doi=10.1073/pnas.1707102114|pmc=5676892|pmid=29078304|doi-access=free}}

{{Main|Spiegelman's monster}}

RNA from Bacteriophage Qβ was used by Sol Spiegelman in experiments that favored faster replication, and thus shorter strands of RNA. He ended up with Spiegelman's Monster, a minimal RNA chain of only 218 nucleotides that can be replicated by Qβ replicase.{{cite book |title=The Ancestor's Tale |isbn=978-0544859937 |last1=Dawkins |author-link=Richard Dawkins |first1=Richard |last2=Wong |first2=Yan |year=2016 |publisher=Houghton Mifflin Harcourt }}

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{{Taxonbar|from1=Q4840022|from2=Q106960755}}

Category:Bacteriophages

Category:Fiersviridae