The T4 Holin Family (TC# 1.E.8) is a group of putative pore-forming proteins that does not belong to one of the seven holin superfamilies. T-even phage such as T4 use a holin-endolysin system for host cell lysis. Although the endolysin of phage T4 encoded by the e gene (Lysozyme E) was identified in 1961, the holin (product of gene t and called T-holin) was not characterized until 2001.[1] A representative list of proteins belonging to the T4 holin family can be found in the Transporter Classification Database.[2]

Structure

T4 holin is fairly large, about 218 amino acyl residues (aas) in length. The protein is highly hydrophilic with 49 acidic and basic residues distributed along its length and a single putative transmembrane segment (TMS) near its N-terminus, leaving most of the protein in the periplasm.[3]

Function

The large periplasmic domain is a major determinant in the timing mechanism and is involved in lysis inhibition (LIN).[4] LIN involves the antiholin rI protein of T4 (See TC# 1.E.8.1.1).[5] Lysis inhibition is an effective strategy to coordinate lysis timing with phage particle maturation and to exclude other phage.[6] The C-terminal periplasmic domain of T4 holin binds the periplasmic domain of T4 antiholin (RI; 97 aas) which like the holin, spans the membrane once.[3] T-holin of T4 phage forms a 1:1 complex with the RI inhibitor which block aggregation and pore formation.[7]

Homology

The phage T4 T-holin (lysis protein) is identical to the holin from phage K3 and nearly identical to that from phage ARI. Residues 35-96 are 28% identical to residues 436-495 of a K+ uptake protein of Lactococcus lactis (gbAAK04721; TC# 2.A.72; KUP), suggesting an evolutionary relationship between a holin and a transporter. Holins have 1 to 4 TMSs and a short C-terminal domain rich in basic residues.

See also

References

  1. Ramanculov, E.; Young, R. (2001-04-01). "Functional analysis of the phage T4 holin in a lambda context". Molecular Genetics and Genomics. 265 (2): 345–353. doi:10.1007/s004380000422. ISSN 1617-4615. PMID 11361346. S2CID 40455691.
  2. "1.E.8 The T4 Holin (T4 Holin) Family". Transporter Classification Database. Retrieved 2016-03-26.
  3. 1 2 Tran, Tram Anh T.; Struck, Douglas K.; Young, Ry (2005-10-01). "Periplasmic domains define holin-antiholin interactions in t4 lysis inhibition". Journal of Bacteriology. 187 (19): 6631–6640. doi:10.1128/JB.187.19.6631-6640.2005. ISSN 0021-9193. PMC 1251592. PMID 16166524.
  4. Ramanculov, E.; Young, R. (2001-03-07). "Genetic analysis of the T4 holin: timing and topology". Gene. 265 (1–2): 25–36. doi:10.1016/s0378-1119(01)00365-1. ISSN 0378-1119. PMID 11255004.
  5. Ramanculov, E.; Young, R. (2001-08-01). "An ancient player unmasked: T4 rI encodes a t-specific antiholin". Molecular Microbiology. 41 (3): 575–583. doi:10.1046/j.1365-2958.2001.02491.x. ISSN 0950-382X. PMID 11532126. S2CID 25273199.
  6. Miller, Eric S.; Kutter, Elizabeth; Mosig, Gisela; Arisaka, Fumio; Kunisawa, Takashi; Rüger, Wolfgang (2003-03-01). "Bacteriophage T4 genome". Microbiology and Molecular Biology Reviews. 67 (1): 86–156, table of contents. doi:10.1128/mmbr.67.1.86-156.2003. ISSN 1092-2172. PMC 150520. PMID 12626685.
  7. Moussa, Samir H.; Kuznetsov, Vladimir; Tran, Tram Anh T.; Sacchettini, James C.; Young, Ry (2012-04-01). "Protein determinants of phage T4 lysis inhibition". Protein Science. 21 (4): 571–582. doi:10.1002/pro.2042. ISSN 1469-896X. PMC 3375757. PMID 22389108.

Further reading

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