Phage spanins: diversity, topological dynamics and gene convergence
Abstract Background Spanins are phage lysis proteins required to disrupt the outer membrane. Phages employ either two-component spanins or unimolecular spanins in this final step of Gram-negative host lysis. Two-component spanins like Rz-Rz1 from phage lambda consist of an integral inner membrane pr...
| Main Authors: | , , , , , , |
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| Format: | Article |
| Language: | English |
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BMC
2018-09-01
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| Series: | BMC Bioinformatics |
| Subjects: | |
| Online Access: | http://link.springer.com/article/10.1186/s12859-018-2342-8 |
| _version_ | 1818145302474915840 |
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| author | Rohit Kongari Manoj Rajaure Jesse Cahill Eric Rasche Eleni Mijalis Joel Berry Ry Young |
| author_facet | Rohit Kongari Manoj Rajaure Jesse Cahill Eric Rasche Eleni Mijalis Joel Berry Ry Young |
| author_sort | Rohit Kongari |
| collection | DOAJ |
| description | Abstract Background Spanins are phage lysis proteins required to disrupt the outer membrane. Phages employ either two-component spanins or unimolecular spanins in this final step of Gram-negative host lysis. Two-component spanins like Rz-Rz1 from phage lambda consist of an integral inner membrane protein: i-spanin, and an outer membrane lipoprotein: o-spanin, that form a complex spanning the periplasm. Two-component spanins exist in three different genetic architectures; embedded, overlapped and separated. In contrast, the unimolecular spanins, like gp11 from phage T1, have an N-terminal lipoylation signal sequence and a C-terminal transmembrane domain to account for the topology requirements. Our proposed model for spanin function, for both spanin types, follows a common theme of the outer membrane getting fused with the inner membrane, effecting the release of progeny virions. Results Here we present a SpaninDataBase which consists of 528 two-component spanins and 58 unimolecular spanins identified in this analysis. Primary analysis revealed significant differences in the secondary structure predictions for the periplasmic domains of the two-component and unimolecular spanin types, as well as within the three different genetic architectures of the two-component spanins. Using a threshold of 40% sequence identity over 40% sequence length, we were able to group the spanins into 143 i-spanin, 125 o-spanin and 13 u-spanin families. More than 40% of these families from each type were singletons, underlining the extreme diversity of this class of lysis proteins. Multiple sequence alignments of periplasmic domains demonstrated conserved secondary structure patterns and domain organization within family members. Furthermore, analysis of families with members from different architecture allowed us to interpret the evolutionary dynamics of spanin gene arrangement. Also, the potential universal role of intermolecular disulfide bonds in two-component spanin function was substantiated through bioinformatic and genetic approaches. Additionally, a novel lipobox motif, AWAC, was identified and experimentally verified. Conclusions The findings from this bioinformatic approach gave us instructive insights into spanin function, evolution, domain organization and provide a platform for future spanin annotation, as well as biochemical and genetic experiments. They also establish that spanins, like viral membrane fusion proteins, adopt different strategies to achieve fusion of the inner and outer membranes. |
| first_indexed | 2024-12-11T12:01:18Z |
| format | Article |
| id | doaj.art-c60df76c6b9643368035cea84344fdbe |
| institution | Directory Open Access Journal |
| issn | 1471-2105 |
| language | English |
| last_indexed | 2024-12-11T12:01:18Z |
| publishDate | 2018-09-01 |
| publisher | BMC |
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| series | BMC Bioinformatics |
| spelling | doaj.art-c60df76c6b9643368035cea84344fdbe2022-12-22T01:08:04ZengBMCBMC Bioinformatics1471-21052018-09-0119112610.1186/s12859-018-2342-8Phage spanins: diversity, topological dynamics and gene convergenceRohit Kongari0Manoj Rajaure1Jesse Cahill2Eric Rasche3Eleni Mijalis4Joel Berry5Ry Young6Center for Phage Technology, Department of Biochemistry and Biophysics, Texas A&M UniversityNational Institutes of HealthCenter for Phage Technology, Department of Biochemistry and Biophysics, Texas A&M UniversityCenter for Phage Technology, Department of Biochemistry and Biophysics, Texas A&M UniversityCenter for Phage Technology, Department of Biochemistry and Biophysics, Texas A&M UniversityUniversity of CaliforniaCenter for Phage Technology, Department of Biochemistry and Biophysics, Texas A&M UniversityAbstract Background Spanins are phage lysis proteins required to disrupt the outer membrane. Phages employ either two-component spanins or unimolecular spanins in this final step of Gram-negative host lysis. Two-component spanins like Rz-Rz1 from phage lambda consist of an integral inner membrane protein: i-spanin, and an outer membrane lipoprotein: o-spanin, that form a complex spanning the periplasm. Two-component spanins exist in three different genetic architectures; embedded, overlapped and separated. In contrast, the unimolecular spanins, like gp11 from phage T1, have an N-terminal lipoylation signal sequence and a C-terminal transmembrane domain to account for the topology requirements. Our proposed model for spanin function, for both spanin types, follows a common theme of the outer membrane getting fused with the inner membrane, effecting the release of progeny virions. Results Here we present a SpaninDataBase which consists of 528 two-component spanins and 58 unimolecular spanins identified in this analysis. Primary analysis revealed significant differences in the secondary structure predictions for the periplasmic domains of the two-component and unimolecular spanin types, as well as within the three different genetic architectures of the two-component spanins. Using a threshold of 40% sequence identity over 40% sequence length, we were able to group the spanins into 143 i-spanin, 125 o-spanin and 13 u-spanin families. More than 40% of these families from each type were singletons, underlining the extreme diversity of this class of lysis proteins. Multiple sequence alignments of periplasmic domains demonstrated conserved secondary structure patterns and domain organization within family members. Furthermore, analysis of families with members from different architecture allowed us to interpret the evolutionary dynamics of spanin gene arrangement. Also, the potential universal role of intermolecular disulfide bonds in two-component spanin function was substantiated through bioinformatic and genetic approaches. Additionally, a novel lipobox motif, AWAC, was identified and experimentally verified. Conclusions The findings from this bioinformatic approach gave us instructive insights into spanin function, evolution, domain organization and provide a platform for future spanin annotation, as well as biochemical and genetic experiments. They also establish that spanins, like viral membrane fusion proteins, adopt different strategies to achieve fusion of the inner and outer membranes.http://link.springer.com/article/10.1186/s12859-018-2342-8Bacteriophage lysisSpaninsMembrane fusionGene evolutionSecondary structure predictionsGenetic architecture |
| spellingShingle | Rohit Kongari Manoj Rajaure Jesse Cahill Eric Rasche Eleni Mijalis Joel Berry Ry Young Phage spanins: diversity, topological dynamics and gene convergence BMC Bioinformatics Bacteriophage lysis Spanins Membrane fusion Gene evolution Secondary structure predictions Genetic architecture |
| title | Phage spanins: diversity, topological dynamics and gene convergence |
| title_full | Phage spanins: diversity, topological dynamics and gene convergence |
| title_fullStr | Phage spanins: diversity, topological dynamics and gene convergence |
| title_full_unstemmed | Phage spanins: diversity, topological dynamics and gene convergence |
| title_short | Phage spanins: diversity, topological dynamics and gene convergence |
| title_sort | phage spanins diversity topological dynamics and gene convergence |
| topic | Bacteriophage lysis Spanins Membrane fusion Gene evolution Secondary structure predictions Genetic architecture |
| url | http://link.springer.com/article/10.1186/s12859-018-2342-8 |
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