Proline isomerization modulates the bacterial IsdB/hemoglobin interaction: an atomic force spectroscopy study
Abstract Iron surface determinant B (IsdB), a Staphylococcus aureus (SA) surface protein involved in both heme iron acquisition from host hemoglobin (Hb) and bacterial adhesion, is a proven virulence factor that can be targeted for the design of antibacterial molecules or vaccines. Recent single-mol...
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| Format: | Article |
| Language: | English |
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Springer
2025-02-01
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| Series: | Discover Nano |
| Online Access: | https://doi.org/10.1186/s11671-025-04182-1 |
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| _version_ | 1823861634476539904 |
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| author | Francesca Pancrazi Omar De Bei Francesco Lavecchia di Tocco Marialaura Marchetti Barbara Campanini Salvatore Cannistraro Stefano Bettati Anna Rita Bizzarri |
| author_facet | Francesca Pancrazi Omar De Bei Francesco Lavecchia di Tocco Marialaura Marchetti Barbara Campanini Salvatore Cannistraro Stefano Bettati Anna Rita Bizzarri |
| author_sort | Francesca Pancrazi |
| collection | DOAJ |
| description | Abstract Iron surface determinant B (IsdB), a Staphylococcus aureus (SA) surface protein involved in both heme iron acquisition from host hemoglobin (Hb) and bacterial adhesion, is a proven virulence factor that can be targeted for the design of antibacterial molecules or vaccines. Recent single-molecule experiments on IsdB interaction with cell adhesion factors revealed an increase of the complex lifetime upon applying a stronger force (catch bond); this was suggested to favor host invasion under shear stress. An increased bond strength under mechanical stress was also detected by Atomic Force Spectroscopy (AFS) for the interaction between IsdB and Hb. Structural information on the underlying molecular mechanisms at the basis of this behaviour in IsdB-based complexes is missing. Here, we show that the single point mutation of Pro173 in the IsdB domain responsible for Hb binding, which weakens the IsdB:Hb interaction without hampering heme extraction, totally abolishes the previously observed behavior. Remarkably, Pro173 does not directly interact with Hb, but undergoes cis–trans isomerization upon IsdB:Hb complex formation, coupled to folding-upon binding of the corresponding protein loop. Our results suggest that these events might represent the molecular basis for the stress-dependence of bond strength observed for wild type IsdB, shedding light on the mechanisms that govern the capability of SA to infect host cells. |
| format | Article |
| id | doaj-art-4be48e8e896443869ac8ed2091f1d4f5 |
| institution | Kabale University |
| issn | 2731-9229 |
| language | English |
| publishDate | 2025-02-01 |
| publisher | Springer |
| record_format | Article |
| series | Discover Nano |
| spelling | doaj-art-4be48e8e896443869ac8ed2091f1d4f52025-02-09T12:51:18ZengSpringerDiscover Nano2731-92292025-02-0120111010.1186/s11671-025-04182-1Proline isomerization modulates the bacterial IsdB/hemoglobin interaction: an atomic force spectroscopy studyFrancesca Pancrazi0Omar De Bei1Francesco Lavecchia di Tocco2Marialaura Marchetti3Barbara Campanini4Salvatore Cannistraro5Stefano Bettati6Anna Rita Bizzarri7Biophysics and Nanoscience Centre, DEB, Università della Tuscia, Largo dell’UniversitàDepartment of Medicine and Surgery, University of ParmaBiophysics and Nanoscience Centre, DEB, Università della Tuscia, Largo dell’UniversitàDepartment of Medicine and Surgery, University of ParmaDepartment of Food and Drug, University of ParmaBiophysics and Nanoscience Centre, DEB, Università della Tuscia, Largo dell’UniversitàDepartment of Medicine and Surgery, University of ParmaBiophysics and Nanoscience Centre, DEB, Università della Tuscia, Largo dell’UniversitàAbstract Iron surface determinant B (IsdB), a Staphylococcus aureus (SA) surface protein involved in both heme iron acquisition from host hemoglobin (Hb) and bacterial adhesion, is a proven virulence factor that can be targeted for the design of antibacterial molecules or vaccines. Recent single-molecule experiments on IsdB interaction with cell adhesion factors revealed an increase of the complex lifetime upon applying a stronger force (catch bond); this was suggested to favor host invasion under shear stress. An increased bond strength under mechanical stress was also detected by Atomic Force Spectroscopy (AFS) for the interaction between IsdB and Hb. Structural information on the underlying molecular mechanisms at the basis of this behaviour in IsdB-based complexes is missing. Here, we show that the single point mutation of Pro173 in the IsdB domain responsible for Hb binding, which weakens the IsdB:Hb interaction without hampering heme extraction, totally abolishes the previously observed behavior. Remarkably, Pro173 does not directly interact with Hb, but undergoes cis–trans isomerization upon IsdB:Hb complex formation, coupled to folding-upon binding of the corresponding protein loop. Our results suggest that these events might represent the molecular basis for the stress-dependence of bond strength observed for wild type IsdB, shedding light on the mechanisms that govern the capability of SA to infect host cells.https://doi.org/10.1186/s11671-025-04182-1 |
| spellingShingle | Francesca Pancrazi Omar De Bei Francesco Lavecchia di Tocco Marialaura Marchetti Barbara Campanini Salvatore Cannistraro Stefano Bettati Anna Rita Bizzarri Proline isomerization modulates the bacterial IsdB/hemoglobin interaction: an atomic force spectroscopy study Discover Nano |
| title | Proline isomerization modulates the bacterial IsdB/hemoglobin interaction: an atomic force spectroscopy study |
| title_full | Proline isomerization modulates the bacterial IsdB/hemoglobin interaction: an atomic force spectroscopy study |
| title_fullStr | Proline isomerization modulates the bacterial IsdB/hemoglobin interaction: an atomic force spectroscopy study |
| title_full_unstemmed | Proline isomerization modulates the bacterial IsdB/hemoglobin interaction: an atomic force spectroscopy study |
| title_short | Proline isomerization modulates the bacterial IsdB/hemoglobin interaction: an atomic force spectroscopy study |
| title_sort | proline isomerization modulates the bacterial isdb hemoglobin interaction an atomic force spectroscopy study |
| url | https://doi.org/10.1186/s11671-025-04182-1 |
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