Architecture of a complete Bce-type antimicrobial peptide resistance module
Abstract Gram-positive bacteria synthesize and secrete antimicrobial peptides that target the essential process of peptidoglycan synthesis. These antimicrobial peptides not only regulate the dynamics of microbial communities but are also of clinical importance as exemplified by peptides such as baci...
| Main Authors: | , |
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2023-07-01
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| Series: | Nature Communications |
| Online Access: | https://doi.org/10.1038/s41467-023-39678-w |
| _version_ | 1797789742115323904 |
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| author | Natasha L. George Benjamin J. Orlando |
| author_facet | Natasha L. George Benjamin J. Orlando |
| author_sort | Natasha L. George |
| collection | DOAJ |
| description | Abstract Gram-positive bacteria synthesize and secrete antimicrobial peptides that target the essential process of peptidoglycan synthesis. These antimicrobial peptides not only regulate the dynamics of microbial communities but are also of clinical importance as exemplified by peptides such as bacitracin, vancomycin, and daptomycin. Many gram-positive species have evolved specialized antimicrobial peptide sensing and resistance machinery known as Bce modules. These modules are membrane protein complexes formed by an unusual Bce-type ABC transporter interacting with a two-component system sensor histidine kinase. In this work, we provide the first structural insight into how the membrane protein components of these modules assemble into a functional complex. A cryo-EM structure of an entire Bce module revealed an unexpected mechanism of complex assembly, and extensive structural flexibility in the sensor histidine kinase. Structures of the complex in the presence of a non-hydrolysable ATP analog reveal how nucleotide binding primes the complex for subsequent activation. Accompanying biochemical data demonstrate how the individual membrane protein components of the complex exert functional control over one another to create a tightly regulated enzymatic system. |
| first_indexed | 2024-03-13T01:54:59Z |
| format | Article |
| id | doaj.art-f0a6a414bf0b46fbabfe22d0e9366b5f |
| institution | Directory Open Access Journal |
| issn | 2041-1723 |
| language | English |
| last_indexed | 2024-03-13T01:54:59Z |
| publishDate | 2023-07-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Nature Communications |
| spelling | doaj.art-f0a6a414bf0b46fbabfe22d0e9366b5f2023-07-02T11:20:30ZengNature PortfolioNature Communications2041-17232023-07-0114111110.1038/s41467-023-39678-wArchitecture of a complete Bce-type antimicrobial peptide resistance moduleNatasha L. George0Benjamin J. Orlando1Dept. of Biochemistry and Molecular Biology, Michigan State UniversityDept. of Biochemistry and Molecular Biology, Michigan State UniversityAbstract Gram-positive bacteria synthesize and secrete antimicrobial peptides that target the essential process of peptidoglycan synthesis. These antimicrobial peptides not only regulate the dynamics of microbial communities but are also of clinical importance as exemplified by peptides such as bacitracin, vancomycin, and daptomycin. Many gram-positive species have evolved specialized antimicrobial peptide sensing and resistance machinery known as Bce modules. These modules are membrane protein complexes formed by an unusual Bce-type ABC transporter interacting with a two-component system sensor histidine kinase. In this work, we provide the first structural insight into how the membrane protein components of these modules assemble into a functional complex. A cryo-EM structure of an entire Bce module revealed an unexpected mechanism of complex assembly, and extensive structural flexibility in the sensor histidine kinase. Structures of the complex in the presence of a non-hydrolysable ATP analog reveal how nucleotide binding primes the complex for subsequent activation. Accompanying biochemical data demonstrate how the individual membrane protein components of the complex exert functional control over one another to create a tightly regulated enzymatic system.https://doi.org/10.1038/s41467-023-39678-w |
| spellingShingle | Natasha L. George Benjamin J. Orlando Architecture of a complete Bce-type antimicrobial peptide resistance module Nature Communications |
| title | Architecture of a complete Bce-type antimicrobial peptide resistance module |
| title_full | Architecture of a complete Bce-type antimicrobial peptide resistance module |
| title_fullStr | Architecture of a complete Bce-type antimicrobial peptide resistance module |
| title_full_unstemmed | Architecture of a complete Bce-type antimicrobial peptide resistance module |
| title_short | Architecture of a complete Bce-type antimicrobial peptide resistance module |
| title_sort | architecture of a complete bce type antimicrobial peptide resistance module |
| url | https://doi.org/10.1038/s41467-023-39678-w |
| work_keys_str_mv | AT natashalgeorge architectureofacompletebcetypeantimicrobialpeptideresistancemodule AT benjaminjorlando architectureofacompletebcetypeantimicrobialpeptideresistancemodule |