RGD Reference Report - New insights on the protein-ligand interaction differences between the two primary cellular retinol carriers. - Rat Genome Database

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New insights on the protein-ligand interaction differences between the two primary cellular retinol carriers.

Authors: Franzoni, L  Cavazzini, D  Rossi, GL  Lucke, C 
Citation: Franzoni L, etal., J Lipid Res. 2010 Jun;51(6):1332-43. Epub 2009 Nov 25.
RGD ID: 6484697
Pubmed: (View Article at PubMed) PMID:19965581
DOI: Full-text: DOI:10.1194/jlr.M002006

The main retinol carriers in the cytosol are the cellular retinol-binding proteins types I and II (CRBP-I and CRBP-II), which exhibit distinct tissue distributions. They play different roles in the maintenance of vitamin A homeostasis and feature a 100-fold difference in retinol affinity whose origin has not been described in detail. NMR-based hydrogen/deuterium exchange measurements show that, while retinol binding endows both proteins with a more rigid structure, many amide protons exchange much faster in CRBP-II than in CRBP-I in both apo and holo form, despite the conserved three-dimensional fold. The remarkable difference in intrinsic stability between the two homologs appears to modulate their binding properties: the stronger retinol binder CRBP-I displays a reduced flexibility of the backbone structure with respect to CRBP-II. This difference must derive from specific evolution-based amino acid substitutions, resulting in additional stabilization of the CRBP-I scaffold: in fact, we identified a number of potential salt bridges on the protein surface as well as several key interactions inside the binding cavity. Furthermore, our NMR data demonstrate that helix alphaII of the characteristic helix-turn-helix motif in the ligand portal region exists in both apo and holo CRBP-II. Hence, the previously proposed model of retinol binding needs to be revised.

Annotation

Gene Ontology Annotations    

Molecular Function

Objects Annotated

Genes (Rattus norvegicus)
Rbp1  (retinol binding protein 1)
Rbp2  (retinol binding protein 2)


Additional Information