View source for Phage f1

Bacteriophage f1 is structurally classified as a class I filamentous phage, and is closely related to the other Ff phages, [[Phage M13]] and phage fd. <ref name='LIB:Bacteriophages'/> <ref name='PMID:10404600'/>

The full sequence is available from NCBI at [http://www.ncbi.nlm.nih.gov/nuccore/J02448 GenBank: J02448.1]

{{Note| Phage f1 can refer to a number of different phages.  '''This page is about phage f1, a ssDNA filamentous phage.'''  However, phage f1 is also the name used for a ssRNA icosahedral phage and phage F1 is another ssDNA phage.}}
== Morphology ==
Phage f1 is a filamentous (rod-shaped) ssDNA phage, with a molecular mass of about 1.6x10<sup>7</sup> Da; by weight it is 11.3 percent DNA. <ref name='PMID:7616570'/> <ref name='PMID:14065763'/>  The flexible phages are about 8500 Å (850 nm) long, and depending on the staining technique, appear to be 43 or 63 Å wide. <ref name='PMID:14065763'/>  The thousands of identical major coat proteins that make up the sheath are slightly curved, enlongated proteins about 70 Å by 10 Å arranged in an α-helix. <ref name='PMID:21082179'/> <ref name='PMID:9631287'/>  These sheath proteins slightly overlap and are oriented just slightly off of perpendicular (20°) to the length of the filament; they are interdigitated and slope radially (with a 5-fold rotation axis and 2-fold helical axis) to form a fishscale-like coating for the DNA core. <ref name='LIB:Bacteriophages'/> <ref name='PMID:21082179'/> 

The ends of the filament are sealed with protein caps.  The end that is extruded first appears blunt and contains 3-5 copies of each [[Phage_f1_VII:Gene_Product(s)| pVII]] and [[Phage_f1_IX:Gene_Product(s)| pIX]], while about 5 copies each of [[Phage_f1_III:Gene_Product(s)| pIII]] and [[Phage_f1_VI:Gene_Product(s)| pVI]] seal off the terminally extruded end and give it a bead-like appearance.<ref name='LIB:Bacteriophages'/> <ref name='PMID:10404600'/>

== Genome Organization ==
f1 has a circular, 6407 bp genome of ss-DNA.

There are 11 genes encoded on the genome; two are overlapping in-frame genes.  Five of the encoded proteins make up the viron, three are needed for synthesis and the rest are for assembly. <ref name='PMID:9224870'/> The genes are generally referred to by Roman numerals I-XI as listed on the [[:Category:Gene_List:Phage_f1| Phage f1]] page.  Genes are in the order [[Phage_f1_II:Gene| II]] [[Phage_f1_X:Gene| (X)]], [[Phage_f1_V:Gene| V]], [[Phage_f1_VII:Gene| VII]], [[Phage_f1_IX:Gene| IX]], [[Phage_f1_VIII:Gene| VIII]], [[Phage_f1_III:Gene| III]], [[Phage_f1_VI:Gene| VI]], [[Phage_f1_I:Gene| I]] [[Phage_f1_XI:Gene| (XI)]], [[Phage_f1_IV:Gene| IV]], intergenic region (IG or IGR). <ref name='LIB:Bacteriophages'/>  The IGR contains the packing signal (PS) as well as sequences that dictate termination, nicking for replication, and the binding of [[Phage_f1_II:Gene_Product(s)| protein II]] and IHF. <ref name='LIB:Bacteriophages'/>

== Life cycle ==

==== Adsorption and Injection ====
f1 is male specific; it only infects Hfr or F+ strains of ''E. coli''. <ref name='PMID:14065763'/>  The host protein [[tolA]], along with [[tolQ]] and [[tolR]], are required for infection and depolymerization of the coat proteins of the phage. <ref name='LIB:Bacteriophages'/> <ref name='PMID:10404600'/>
The N2 domain of [[Phage_f1_III:Gene_Product(s)| pIII]] binds to the primary receptor, the tip of the F pilus, and retraction of the pilus by an unknown mechanism brings the N1 domain of [[Phage_f1_III:Gene_Product(s)|pIII]] close enough to the membrane to bind the coreceptor [[tolA]].<ref name='PMID:10404600'/> 

The removal of the cap proteins and release of the ssDNA into the cytoplasm are both mediated by the interactions of [[tolA]] and [[Phage_f1_III:Gene_Product(s)| pIII]]. <ref name='PMID:16373072'/>  At least one [[Phage_f1_III:Gene_Product(s)| pIII]] undergoes a conformational change in the C domain as a result of the N1/[[tolA]]  interaction; the hydrophobic portion of [[Phage_f1_III:Gene_Product(s)| pIII]] is revealed and inserts itself into the inner membrane.  <ref name='PMID:16373072'/>  This fastens the viron to the host and allows for the depolymerization of adjacent [[Phage_f1_VIII:Gene_Product(s)| pVIII]], which are distributed into the membrane. <ref name='PMID:16373072'/>  It is the degradation of the major coat protein that causes the genome to be released into the cytoplasm of the host.<ref name='PMID:16373072'/>

==== DNA replication ====
The ssDNA genome is replicated and translated with host enzymes after it is inserted into the cytoplasm.  RNA polymerase creates a primer on the existing (+) strand in the IGR region due to the strong promoter-like signals from -35 and -10 motifs on two hairpin sequences that are stronger than host promoter signals. <ref name='LIB:Bacteriophages'/>  Host DNA polymerase III replicates the remainder of the strand to create a dsDNA product that is further processed by host gyrase to form a supercoiled RF template used for replication. <ref name='LIB:Bacteriophages'/> 

Phage [[Phage_f1_II:Gene_Product(s)|pII]] specifically cuts the (+) strand at the origin, and the genome is replicated from 3' end of the template (-) strand using rolling circle replication, with host Rep helicase displacing the (+) strand. <ref name='LIB:Bacteriophages'/> The [[Phage_f1_II:Gene_Product(s)|pII]] protein is also necessary for ligation of the newly isolated (+) strand, which is replicated in the same manner as the original ssDNA genome. <ref name='LIB:Bacteriophages'/>  Host enzymes are also necessary to translate the phage proteins.

Phage proteins can be detected in the supernatant about 10 minutes after infection (37°). <ref name='LIB:Bacteriophages'/> 

==== Packaging ====
Exponential accumulation of the phage proteins, including [[Phage_f1_V:Gene_Product(s)| pV]], allows for the formation of a DNA-[[Phage_f1_V:Gene_Product(s)| pV]] complex, hundreds of which can form per host. <ref name='LIB:Bacteriophages'/> <ref name='PMID:10404600'/>  The complexes prevent further copies of the complement strand from being made, and also "pre-package" and stabilize the ssDNA into an almost linear form.<ref name='LIB:Bacteriophages'/> <ref name='PMID:10404600'/>   About 1500 copies of [[Phage_f1_V:Gene_Product(s)| pV]], which are dimers at physiological salt concentrations, form a flexible, semi-enclosed left-handed helix about 8x800-900 nm that encapsulate the DNA. <ref name='LIB:Bacteriophages'/> <ref name='PMID:10404600'/> <ref name='PMID:9224870'/> The ssDNA does not interact with itself inside the capsule, and remains untwisted and unpaired except for the extremely stable packing signal.<ref name='LIB:Bacteriophages'/>  The PS exists as an imperfect hairpin and is responsible for the attachment and orientation of the genome in the phage. <ref name='LIB:Bacteriophages'/> Proper packing can be accomplished if and only if the PS is present; even after the genome has been covered it remains partially exposed at the blunt end of the complex. <ref name='LIB:Bacteriophages'/>

==== Lysis ====
This phage does not lyse its host, but can secrete many copies of itself throughout the life of the host cell.  The phage are secreted as they are assembled, and once the [[Phage_f1_V:Gene_Product(s)| pV]]-DNA complex is formed all further assembly and secretion steps take place in or at a membrane. <ref name='PMID:9224870'/>  The proteins depolymerized upon phage entry can be reused for the packaging of new phage, and as with newly synthesized coat proteins [[Phage_f1_III:Gene_Product(s)| pIII]], [[Phage_f1_VI:Gene_Product(s)| pVI]], [[Phage_f1_VII:Gene_Product(s)| pVII]], [[Phage_f1_VIII:Gene_Product(s)| pVIII]] and [[Phage_f1_IX:Gene_Product(s)| pIX]], the proteins remain as integral membrane proteins until needed. <ref name='LIB:Bacteriophages'/>  

Both [[Phage_f1_I:Gene_Product(s)| pI]] and [[Phage_f1_XI:Gene_Product(s)| pXI]] span the cytoplasmic membrane; together with the outer membrane protein [[Phage_f1_IV:Gene_Product(s)| pIV]] they create distinct assembly sites (adhesion zones) where the membranes are close together.  <ref name='LIB:Bacteriophages'/>  It is possible that [[Phage_f1_IV:Gene_Product(s)| pIV]] multimers form controlled channels for the export of nascent phage, although the exact mechanism for phage exit is unclear. <ref name='PMID:9224870'/>  The PS is likely recognized by [[Phage_f1_I:Gene_Product(s)| pI]]; this protein might also bind thioredoxin and promote the addition of [[Phage_f1_VIII:Gene_Product(s)| pVIII]] to the elongating phage.  <ref name='PMID:9224870'/> 

The host-encoded thioredoxin is the only known host protein required for assembly of nascent phage and likely confers processivity. <ref name='PMID:9224870'/> <ref name='LIB:Bacteriophages'/> The presence of a properly presented ssDNA in an adhesion zone with thioredoxin, [[Phage_f1_VIII:Gene_Product(s)| major coat protein]], and the minor coat proteins [[Phage_f1_XI:Gene_Product(s)| pXI]] and [[Phage_f1_I:Gene_Product(s)| pI]] allows for the elongation and secretion of phages. <ref name='LIB:Bacteriophages'/>.  The phage is enlongated by continually removing [[Phage_f1_V:Gene_Product(s)| pV]] dimers and replacing them with the major coat protein.  The phage coat consists of about 2700 copies of the [[Phage_f1_VIII:Gene_Product(s)| major coat protein]] encoded by [[Phage_f1_VIII:Gene_Product(s)| pVIII]]. <ref name='PMID:9636697'/> 

The end of the DNA signals the cell to add [[Phage_f1_VI:Gene_Product(s)| pVI]] and [[Phage_f1_III:Gene_Product(s)| pIII]], which are likely already associated with the [[Phage_f1_VIII:Gene_Product(s)| major coat protein]].  A modified 132-residue form of [[Phage_f1_III:Gene_Product(s)| pIII]] is required for stabilization of the phage, while a shorter 93-residue (also the C-terminal portion) is sufficient for release and the last 83-residue portion of the C-terminal is capable of binding [[Phage_f1_VI:Gene_Product(s)| pVI]]. <ref name='LIB:Bacteriophages'/> <ref name='PMID:7616570'/>  
As with most filamentous phages, there is no defined limit on the amount of DNA that can be packaged into the phage coat (contrast to phages with set capsid size, such as [[Bacteriophage_λ| phage λ]]).  <ref name='LIB:Bacteriophages'/>  Excessive copies of the phage genome can be packaged, called "polyphage"; although these are due to improper termination of extrusion about 5% of the phage produced in the presence of termination signals are twice the normal length. <ref name='LIB:Bacteriophages'/> Even larger inserts are naturally selected against. <ref name='LIB:Bacteriophages'/>  The non-terminated phage will remain anchored to the host, and attachment of another [[Phage_f1_V:Gene_Product(s)| pV]]-DNA complex will continue the enlongation process.<ref name='LIB:Bacteriophages'/>  The PS site is only needed to initiate enlongation, not for the attachment of additional genomes.<ref name='LIB:Bacteriophages'/>

Another domain of [[Phage_f1_III:Gene_Product(s)| pIII]] is responsible for defects in the outer membrane, which result in the seepage of periplasmic contents and increase the host's susceptibility to detergents. <ref name='LIB:Bacteriophages'/>

== See also ==
* [[Phage_M13]]
* [http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?id=10861 phage f1 taxonomy on NCBI]
* [http://www.ictvdb.org/ ICTV - International Committee on Taxonomy of Viruses]

== References ==
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