Holin

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. 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 proteins called viroporins to permeabilize the host's membrane. According to their structure there are three main classes of 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 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. 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. According to the Transporter Classification Database, there are a total of seven holin superfamilies.