Role of cis-trans proline isomerization in the function of pathogenic enterobacterial Periplasmic Binding Proteins.
Periplasmic Binding Proteins (PBPs) trap nutrients for their internalization into bacteria by ABC transporters. Ligand binding triggers PBP closure by bringing its two domains together like a Venus flytrap. The atomic determinants that control PBP opening and closure for nutrient capture and release...
| Main Authors: | , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Public Library of Science (PLoS)
2017-01-01
|
| Series: | PLoS ONE |
| Online Access: | http://europepmc.org/articles/PMC5708682?pdf=render |
| _version_ | 1818541014819799040 |
|---|---|
| author | Paulina Cortes-Hernandez Lenin Domínguez-Ramírez |
| author_facet | Paulina Cortes-Hernandez Lenin Domínguez-Ramírez |
| author_sort | Paulina Cortes-Hernandez |
| collection | DOAJ |
| description | Periplasmic Binding Proteins (PBPs) trap nutrients for their internalization into bacteria by ABC transporters. Ligand binding triggers PBP closure by bringing its two domains together like a Venus flytrap. The atomic determinants that control PBP opening and closure for nutrient capture and release are not known, although it is proposed that opening and ligand release occur while in contact with the ABC transporter for concurrent substrate translocation. In this paper we evaluated the effect of the isomerization of a conserved proline, located near the binding site, on the propensity of PBPs to open and close. ArgT/LAO from Salmonella typhimurium and HisJ from Escherichia coli were studied through molecular mechanics at two different temperatures: 300 and 323 K. Eight microseconds were simulated per protein to analyze protein opening and closure in the absence of the ABC transporter. We show that when the studied proline is in trans, closed empty LAO and HisJ can open. In contrast, with the proline in cis, opening transitions were much less frequent and characterized by smaller changes. The proline in trans also renders the open trap prone to close over a ligand. Our data suggest that the isomerization of this conserved proline modulates the PBP mechanism: the proline in trans allows the exploration of conformational space to produce trap opening and closure, while in cis it restricts PBP movement and could limit ligand release until in productive contact with the ABC transporter. This is the first time that a proline isomerization has been related to the control of a large conformational change like the PBP flytrap mechanism. |
| first_indexed | 2024-12-11T22:02:59Z |
| format | Article |
| id | doaj.art-f4075f6b8bc24f5fbf7857bd30261b62 |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-12-11T22:02:59Z |
| publishDate | 2017-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-f4075f6b8bc24f5fbf7857bd30261b622022-12-22T00:49:02ZengPublic Library of Science (PLoS)PLoS ONE1932-62032017-01-011211e018893510.1371/journal.pone.0188935Role of cis-trans proline isomerization in the function of pathogenic enterobacterial Periplasmic Binding Proteins.Paulina Cortes-HernandezLenin Domínguez-RamírezPeriplasmic Binding Proteins (PBPs) trap nutrients for their internalization into bacteria by ABC transporters. Ligand binding triggers PBP closure by bringing its two domains together like a Venus flytrap. The atomic determinants that control PBP opening and closure for nutrient capture and release are not known, although it is proposed that opening and ligand release occur while in contact with the ABC transporter for concurrent substrate translocation. In this paper we evaluated the effect of the isomerization of a conserved proline, located near the binding site, on the propensity of PBPs to open and close. ArgT/LAO from Salmonella typhimurium and HisJ from Escherichia coli were studied through molecular mechanics at two different temperatures: 300 and 323 K. Eight microseconds were simulated per protein to analyze protein opening and closure in the absence of the ABC transporter. We show that when the studied proline is in trans, closed empty LAO and HisJ can open. In contrast, with the proline in cis, opening transitions were much less frequent and characterized by smaller changes. The proline in trans also renders the open trap prone to close over a ligand. Our data suggest that the isomerization of this conserved proline modulates the PBP mechanism: the proline in trans allows the exploration of conformational space to produce trap opening and closure, while in cis it restricts PBP movement and could limit ligand release until in productive contact with the ABC transporter. This is the first time that a proline isomerization has been related to the control of a large conformational change like the PBP flytrap mechanism.http://europepmc.org/articles/PMC5708682?pdf=render |
| spellingShingle | Paulina Cortes-Hernandez Lenin Domínguez-Ramírez Role of cis-trans proline isomerization in the function of pathogenic enterobacterial Periplasmic Binding Proteins. PLoS ONE |
| title | Role of cis-trans proline isomerization in the function of pathogenic enterobacterial Periplasmic Binding Proteins. |
| title_full | Role of cis-trans proline isomerization in the function of pathogenic enterobacterial Periplasmic Binding Proteins. |
| title_fullStr | Role of cis-trans proline isomerization in the function of pathogenic enterobacterial Periplasmic Binding Proteins. |
| title_full_unstemmed | Role of cis-trans proline isomerization in the function of pathogenic enterobacterial Periplasmic Binding Proteins. |
| title_short | Role of cis-trans proline isomerization in the function of pathogenic enterobacterial Periplasmic Binding Proteins. |
| title_sort | role of cis trans proline isomerization in the function of pathogenic enterobacterial periplasmic binding proteins |
| url | http://europepmc.org/articles/PMC5708682?pdf=render |
| work_keys_str_mv | AT paulinacorteshernandez roleofcistransprolineisomerizationinthefunctionofpathogenicenterobacterialperiplasmicbindingproteins AT lenindominguezramirez roleofcistransprolineisomerizationinthefunctionofpathogenicenterobacterialperiplasmicbindingproteins |