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- Title
Characterization of the molten globule state of retinol-binding protein using a molecular dynamics simulation approach.
- Authors
Paci, Emanuele; Greene, Lesley H.; Jones, Rachel M.; Smith, Lorna J.
- Abstract
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 Å greater than that of the native state, contain on average 37%β-sheet secondary structure. In these conformers the central regions of the two orthogonal β-sheets that make up the β-barrel in the native protein are highly persistent. However, there are sizable fluctuations for residues in the outer regions of the β-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 (β-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.
- Subjects
MOLECULAR dynamics; DYNAMICS; PROTEIN folding; PROTEIN conformation; VITAMIN A; PROTEIN binding; CAROTENES; BIOCHEMISTRY
- Publication
FEBS Journal, 2005, Vol 272, Issue 18, p4826
- ISSN
1742-464X
- Publication type
Article
- DOI
10.1111/j.1742-4658.2005.04898.x