Characterization of the molten globule state of retinol-binding protein using a molecular dynamics simulation approach.
Retinol-binding protein transports retinol, and circulates in the plasma as a macromolecular complex with the protein transthyretin. Under acidic conditions retinol-binding protein undergoes a transition to the molten globule state, and releases the bound retinol ligand. A biased molecular dynamics...
| Main Authors: | , , , |
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| Format: | Journal article |
| Language: | English |
| Published: |
2005
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| _version_ | 1797062696152072192 |
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| author | Paci, E Greene, L Jones, R Smith, L |
| author_facet | Paci, E Greene, L Jones, R Smith, L |
| author_sort | Paci, E |
| collection | OXFORD |
| description | Retinol-binding protein transports retinol, and circulates in the plasma as a macromolecular complex with the protein transthyretin. Under acidic conditions retinol-binding protein undergoes a transition to the molten globule state, and releases the bound retinol ligand. A biased molecular dynamics simulation method has been used to generate models for the ensemble of conformers populated within this molten globule state. Simulation conformers, with a radius of gyration at least 1.1 A greater than that of the native state, contain on average 37%beta-sheet secondary structure. In these conformers the central regions of the two orthogonal beta-sheets that make up the beta-barrel in the native protein are highly persistent. However, there are sizable fluctuations for residues in the outer regions of the beta-sheets, and large variations in side chain packing even in the protein core. Significant conformational changes are seen in the simulation conformers for residues 85-104 (beta-strands E and F and the E-F loop). These changes give an opening of the retinol-binding site. Comparisons with experimental data suggest that the unfolding in this region may provide a mechanism by which the complex of retinol-binding protein and transthyretin dissociates, and retinol is released at the cell surface. |
| first_indexed | 2024-03-06T20:49:15Z |
| format | Journal article |
| id | oxford-uuid:37042c72-9f03-4d2d-a538-932b01c4862d |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-06T20:49:15Z |
| publishDate | 2005 |
| record_format | dspace |
| spelling | oxford-uuid:37042c72-9f03-4d2d-a538-932b01c4862d2022-03-26T13:41:22ZCharacterization of the molten globule state of retinol-binding protein using a molecular dynamics simulation approach.Journal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:37042c72-9f03-4d2d-a538-932b01c4862dEnglishSymplectic Elements at Oxford2005Paci, EGreene, LJones, RSmith, LRetinol-binding protein transports retinol, and circulates in the plasma as a macromolecular complex with the protein transthyretin. Under acidic conditions retinol-binding protein undergoes a transition to the molten globule state, and releases the bound retinol ligand. A biased molecular dynamics simulation method has been used to generate models for the ensemble of conformers populated within this molten globule state. Simulation conformers, with a radius of gyration at least 1.1 A greater than that of the native state, contain on average 37%beta-sheet secondary structure. In these conformers the central regions of the two orthogonal beta-sheets that make up the beta-barrel in the native protein are highly persistent. However, there are sizable fluctuations for residues in the outer regions of the beta-sheets, and large variations in side chain packing even in the protein core. Significant conformational changes are seen in the simulation conformers for residues 85-104 (beta-strands E and F and the E-F loop). These changes give an opening of the retinol-binding site. Comparisons with experimental data suggest that the unfolding in this region may provide a mechanism by which the complex of retinol-binding protein and transthyretin dissociates, and retinol is released at the cell surface. |
| spellingShingle | Paci, E Greene, L Jones, R Smith, L Characterization of the molten globule state of retinol-binding protein using a molecular dynamics simulation approach. |
| title | Characterization of the molten globule state of retinol-binding protein using a molecular dynamics simulation approach. |
| title_full | Characterization of the molten globule state of retinol-binding protein using a molecular dynamics simulation approach. |
| title_fullStr | Characterization of the molten globule state of retinol-binding protein using a molecular dynamics simulation approach. |
| title_full_unstemmed | Characterization of the molten globule state of retinol-binding protein using a molecular dynamics simulation approach. |
| title_short | Characterization of the molten globule state of retinol-binding protein using a molecular dynamics simulation approach. |
| title_sort | characterization of the molten globule state of retinol binding protein using a molecular dynamics simulation approach |
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