5H8T

Crystal structure of human cellular retinol binding protein 1 in complex with all-trans-retinol

Summary for 5H8T

• Entry DOI: 10.2210/pdb5h8t/pdb
• Related: 1CRB 5H9A 5HA1 5HBS
• Descriptor: Retinol-binding protein 1, RETINOL (3 entities in total)
• Functional Keywords: vitamin a, retinol, binding protein, retinol-binding protein
• Biological source: Homo sapiens (Human)
• Total number of polymer chains: 1
• Total formula weight: 16855.32

Authors

Golczak, M.,Arne, J.M.,Silvaroli, J.A.,Kiser, P.D.,Banerjee, S. (deposition date: 2015-12-23, release date: 2016-03-02, Last modification date: 2023-09-27)

Primary citation

Silvaroli, J.A.,Arne, J.M.,Chelstowska, S.,Kiser, P.D.,Banerjee, S.,Golczak, M.
Ligand Binding Induces Conformational Changes in Human Cellular Retinol-binding Protein 1 (CRBP1) Revealed by Atomic Resolution Crystal Structures.
J.Biol.Chem., 291:8528-8540, 2016

PubMed Abstract: Important in regulating the uptake, storage, and metabolism of retinoids, cellular retinol-binding protein 1 (CRBP1) is essential for trafficking vitamin A through the cytoplasm. However, the molecular details of ligand uptake and targeted release by CRBP1 remain unclear. Here we report the first structure of CRBP1 in a ligand-free form as well as ultra-high resolution structures of this protein bound to either all-trans-retinol or retinylamine, the latter a therapeutic retinoid that prevents light-induced retinal degeneration. Superpositioning of human apo- and holo-CRBP1 revealed major differences within segments surrounding the entrance to the retinoid-binding site. These included α-helix II and hairpin turns between β-strands βC-βD and βE-βF as well as several side chains, such as Phe-57, Tyr-60, and Ile-77, that change their orientations to accommodate the ligand. Additionally, we mapped hydrogen bond networks inside the retinoid-binding cavity and demonstrated their significance for the ligand affinity. Analyses of the crystallographic B-factors indicated several regions with higher backbone mobility in the apoprotein that became more rigid upon retinoid binding. This conformational flexibility of human apo-CRBP1 facilitates interaction with the ligands, whereas the more rigid holoprotein structure protects the labile retinoid moiety during vitamin A transport. These findings suggest a mechanism of induced fit upon ligand binding by mammalian cellular retinol-binding proteins.

PubMed: 26900151
DOI: 10.1074/jbc.M116.714535

Experimental method

X-RAY DIFFRACTION (1.21 Å)