T4 holin

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

• Holin
• Lysin
• Transporter Classification Database

References

1. Ramanculov, E.; Young, R. (2001-04-01). "Functional analysis of the phage T4 holin in a lambda context". Molecular Genetics and Genomics: MGG. 265 (2): 345–353. doi:10.1007/s004380000422. ISSN 1617-4615. PMID 11361346.
2. "1.E.8 The T4 Holin (T4 Holin) Family". Transporter Classification Database. Retrieved 2016-03-26.
3. 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.
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

• Catalão MJ, Gil F, Moniz-Pereira J, São-José C, Pimentel M (2013). "Diversity in bacterial lysis systems: bacteriophages show the way". FEMS Microbiology Reviews. 37 (4): 554–571. doi:10.1111/1574-6976.12006. PMID 23043507.
• Moussa SH, Lawler JL, Young R (2014). "Genetic Dissection of T4 Lysis". Journal of Bacteriology. 196 (12): 2201–2209. doi:10.1128/JB.01548-14. PMC 4054191. PMID 24706740.
• Saier MH, Reddy BL, Margolin W (2015). "Holins in Bacteria, Eukaryotes, and Archaea: Multifunctional Xenologues with Potential Biotechnological and Biomedical Applications". Journal of Bacteriology. 197 (1): 7–17. doi:10.1128/JB.02046-14. PMC 4288690. PMID 25157079.
• Tran TA, Struck DK, Young R (2005). "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. PMC 1251592. PMID 16166524.
• Tran TA, Struck DK, Young R (2007). "The T4 RI Antiholin Has an N-Terminal Signal Anchor Release Domain That Targets It for Degradation by DegP". Journal of Bacteriology. 189 (21): 7618–7625. doi:10.1128/JB.00854-07. PMC 2168732. PMID 17693511.
• Wang I, Smith DL, Young R (2000). "Holins: The Protein Clocks of Bacteriophage Infections". Annual Review of Microbiology. 54 (1): 799–825. doi:10.1146/annurev.micro.54.1.799. PMID 11018145.

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