A signal-arrest-release sequence mediates export and control of the phage P1 endolysin

Xu, Min; Struck, Douglas K.; Deaton, John; Wang, Ing-Nang; Young, Ry

doi:10.1073/pnas.0400957101

Cited by 150 publications

(210 citation statements)

References 34 publications

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“…Although the processing of endolysin was observed in many other bacteriophages, there are some exceptions wherein the SAR sequence is not cleaved by the periplasmic protease. E. coli bacteriophage P1 lysin, for example, showed the presence of N-terminal SAR sequence when its periplasmic and cytoplasmic fractions were tested on SDS-PAGE, suggesting that the SAR sequence remains attached to the endolysin even after export (Xu et al, 2004). Similar observations were made for Erwinia amylovora phage ERA103 and other bacteriophages (Kuty et al, 2010;Briers et al, 2011).…”

Section: Regulation During Translocationsupporting

confidence: 67%

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Insights into the regulation of bacteriophage endolysin: multiple means to the same end

Pohane¹,

Jain²

2015

Microbiology

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Antibiotics are the molecules of choice to treat bacterial infections. However, because of the rapid emergence of drug-resistant bacteria, alternative modes of combating infections are being envisaged. Bacteriophages, which infect and lyse bacterial cells, may function as effective antimicrobial agents. Most bacteriophages produce their own peptidoglycan hydrolase called endolysin or lysin, which breaks down the cell wall of bacteria and aids in the release of newly assembled virions. Here, we discuss several findings that help us in understanding how endolysins are regulated. We observe that there is no common mechanism that is followed in all cases. Many different modes of activity regulation have been observed in endolysins, including regulation of protein expression, translocation across the cell membrane and post-translational modifications. These processes not only demonstrate how endolysins are made dependent on other accessory proteins and non-protein factors for their synthesis, translocation across the cytoplasmic membrane and activity, but also show how autoregulation helps in maintaining the enzyme in an inactive form. Various regulatory mechanisms that are discussed are particularly applicable to endolysins. Nevertheless, a detailed study of these methods opens new avenues of investigation in the area of protein translocation systems and the novel ways of enzyme activation and regulation in bacteria.

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Section: Regulation During Translocationsupporting

confidence: 67%

“…How do these endolysins block their active site? In the case of coliphage 21 endolysin (R 21 ), although a SAR domain is present at the N terminus of endolysin, it lacks a Cys residue (Xu et al, 2004). When the SAR-truncated derivative of R 21 was prepared, it showed no activity in vitro.…”

Section: Regulation By Inactivationmentioning

confidence: 99%

Insights into the regulation of bacteriophage endolysin: multiple means to the same end

Pohane¹,

Jain²

2015

Microbiology

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“…Activation of SAR lysozymes requires their release from the bilayer (8). In these cases, holins are not essential for lysis but are thought to impose timing on the lytic event, because holin triggering depolarizes the membrane, and depolarization accelerates the release of the SAR lysozyme from the bilayer (7).…”

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confidence: 99%

“…For phages like and T4, this allows release of an active lysozyme that has accumulated in the cytosol, and holin function is absolutely required for lysis. For others, like P1 and the lambdoid phage 21, the lysozyme is exported by the host sec system and accumulates in the periplasm as an enzymatically inactive form tethered to the membrane by an N-terminal SAR (''signal anchor-release'') sequence (7,8). Unlike canonical transmembrane domains (TMDs), SAR domains have the unique property of escaping from the bilayer, in part because of an elevated content of relatively nonhydrophobic residues like Gly, Ala, Ser, and Thr (Fig.…”

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confidence: 99%

Topological dynamics of holins in programmed bacterial lysis

Park

Struck

Deaton

et al. 2006

Proc. Natl. Acad. Sci. U.S.A.

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102

164

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The fate of phage-infected bacteria is determined by the holin, a small membrane protein that triggers to disrupt the membrane at a programmed time, allowing a lysozyme to attack the cell wall. S 21 68, the holin of phage 21, has two transmembrane domains (TMDs) with a predicted N-in, C-in topology. Surprisingly, TMD1 of S 21 68 was found to be dispensable for function, to behave as a SAR (''signal-anchor-release'') domain in exiting the membrane to the periplasm, and to engage in homotypic interactions in the soluble phase. The departure of TMD1 from the bilayer coincides with the lethal triggering of the holin and is accelerated by membrane depolarization. Basic residues added at the N terminus of S 21 68 prevent the escape of TMD1 to the periplasm and block hole formation by TMD2. Lysis thus depends on dynamic topology, in that removal of the inhibitory TMD1 from the bilayer frees TMD2 for programmed formation of lethal membrane lesions.bacteriophage ͉ GxxxG motif ͉ SAR domain ͉ transmembrane domain

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“…Endolysins accumulate in the periplasm tethering to the membrane in an enzymically inactive form until the membrane is disrupted by the holin. They are then released from the membrane to the cell wall and convert into an enzymically active form (Xu et al, 2004(Xu et al, , 2005. The regulation of endolysins bearing the SAR domain from the membranetethered inactive form to the active form has been reported (Baase et al, 2010;Kuty et al, 2010;Sun et al, 2009).…”

Section: Introductionmentioning

confidence: 99%

Roles of bacteriophage GVE2 endolysin in host lysis at high temperatures

Jin

Zhang

2013

Microbiology

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The holin-endolysin system is used by double-stranded DNA phages to lyse their bacterial hosts at the terminal stage of the phage reproduction cycle. Endolysins are proteins with one of several muralytic activities able to digest the bacterial cell wall for phage progeny release. However, the functions of thermophilic bacteriophage endolysin in host lysis have not been extensively investigated. In this study, the roles of the endolysin of a thermophilic bacteriophage, GVE2, from a deep-sea hydrothermal vent, which could infect Geobacillus sp. E263 at high temperatures, were characterized. The results showed that GVE2 could lead to lysis of host cells. The confocal microscopy data showed that GFP-endolysin aggregated in GVE2-infected Geobacillus sp. E263 cells, showing the involvement of endolysin in the lysis process at high temperatures. The results revealed that the GVE2 endolysin and holin interacted directly. It was found that the endolysin could interact with the host protein ABC transporter, suggesting that host proteins might participate in the regulation of the lysis process. Therefore, our study presents a novel insight into the mechanism of the lysis process of a thermophilic bacterium by its phage at high temperatures, which should be helpful in revealing the roles of thermophilic bacteriophages in the biosphere of deep-sea hydrothermal vents.

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A signal-arrest-release sequence mediates export and control of the phage P1 endolysin

Cited by 150 publications

References 34 publications

Insights into the regulation of bacteriophage endolysin: multiple means to the same end

Insights into the regulation of bacteriophage endolysin: multiple means to the same end

Topological dynamics of holins in programmed bacterial lysis

Roles of bacteriophage GVE2 endolysin in host lysis at high temperatures

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