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Holin

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Diverse group of small proteins

Holins are a diverse group of small proteins produced by dsDNA bacteriophages in order to trigger and control the degradation of the host's cell wall at the end of the lytic cycle. Holins form pores in the host's cell membrane, allowing lysins to reach and degrade peptidoglycan, a component of bacterial cell walls. Holins have been shown to regulate the timing of lysis with great precision. Over 50 unrelated gene families encode holins, making them the most diverse group of proteins with common function. Together with lysins, holins are being studied for their potential use as antibacterial agents.

While canonical holins act by forming large pores, pinholins such as the S protein of lambdoid phage 21 act by forming heptameric channels that depolarize the bacterial membrane. They are associated with SAR endolysins, which remain inactive in the periplasm prior to the depolarization of the membrane.

Viruses that infect eukaryotic cells may use similar channel-forming proteins called viroporins.

Classification

Structure

According to their structure there are three main classes of holins.

Class I holins

Class I holins have three transmembrane domains (TMDs) with the N-terminus in the periplasm and the C-terminus in the cytoplasm. They generally have over 95 residues. Examples of class I holins include the bacteriophage λ S protein (λ holin) and the Staphylococcus aureus phage P68 hol15 protein.

Class II holins

Class II holins have two TMDs, with both the N- and the C-terminus in the cytoplasm. Their number of residues usually falls between 65 and 95. Examples include the S protein from lambdoid phage 21 and the Hol3626 protein from Clostridium perfringens bacteriophage Ф3626.

Class III holins

Unlike class I and class II holins, which are composed of hydrophobic transmembrane helices, class III holins form a single highly hydrophilic TMD, with the N-terminus in the cytoplasm and the C-terminus in the periplasm. The first class III holin to be characterized was the bacteriophage T4-encoded t protein (T4 holin). Other examples include the holins of the ФCP39O and ФCP26F phage.

Gene families

According to the Transporter Classification Database, there are a total of seven holin superfamilies.

There are also several holin families that do not fall into the superfamilies designated above. These families include:

See also

References

  1. Wang IN, Smith DL, Young R (2002). "Holins: the protein clocks of bacteriophage infections". Annu Rev Microbiol. 54: 799–825. doi:10.1146/annurev.micro.54.1.799. PMID 11018145.
  2. Gründling A, Manson MD, Young R (July 2001). "Holins kill without warning". Proc. Natl. Acad. Sci. U.S.A. 98 (16): 9348–9352. doi:10.1073/pnas.151247598. PMC 55423. PMID 11459934.
  3. ^ Young R (January 2002). "Bacteriophage Holins: Deadly Diversity" (PDF). J. Mol. Microbiol. Biotechnol. 4 (1): 21–36. PMID 11763969.
  4. Veiga-Crespo P; Barros-Velázquez J; Villa T.G. (2007). Méndez-Vilas A (ed.). "What can bacteriophages do for us?" (PDF). Communicating Current Research and Educational Topics and Trends in Applied Microbiology: 885–893. Archived from the original (PDF) on 2016-03-03. Retrieved 2013-11-09.
  5. Young, Ryland (1 March 2014). "Phage lysis: Three steps, three choices, one outcome". Journal of Microbiology. 52 (3): 243–258. doi:10.1007/s12275-014-4087-z. PMC 4012431. PMID 24585055.
  6. Nieva, José Luis; Madan, Vanesa; Carrasco, Luis (2 July 2012). "Viroporins: structure and biological functions". Nature Reviews Microbiology. 10 (8): 563–574. doi:10.1038/nrmicro2820. hdl:10261/115331. PMC 7097105. PMID 22751485.
  7. Nieva, José; Carrasco, Luis (29 September 2015). "Viroporins: Structures and functions beyond cell membrane permeabilization". Viruses. 7 (10): 5169–5171. doi:10.3390/v7102866. PMC 4632374. PMID 26702461.
  8. ^ Shi Y, Yan Y, Ji W, Du B, Meng X, Wang H, Sun J (March 2012). "Characterization and determination of holin protein of Streptococcus suis bacteriophage SMP in heterologous host". Virology Journal. 9: 70. doi:10.1186/1743-422X-9-70. PMC 3359269. PMID 22436471.
  9. ^ Ramanculov E, Young R (March 2001). "Genetic analysis of the T4 holin: timing and topology". Gene. 265 (1–2): 25–36. doi:10.1016/S0378-1119(01)00365-1. PMID 11255004.
  10. Saier M. "TC-Superfamilies". Transporter Classification Database. Retrieved 9 November 2013.

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