Molecular basis for the interaction of cellular retinol binding protein 2 (CRBP2) with nonretinoid ligands
| Autor: | Jacqueline Plau, Josie A. Silvaroli, William S. Blaner, Marcin Golczak, Charlie H. Adams, Made Airanthi K. Widjaja-Adhi, Surajit Banerjee |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
0301 basic medicine
2-AGE 2-arachidonoyl glycerol ether 1-ASG arachidonoyl-1-thioglycerol Protein Data Bank (RCSB PDB) 030204 cardiovascular system & hematology acyl chain AEA arachidonyl ethanolamine HTS high-throughput screening Biochemistry Interactome cellular retinol binding protein 2 0302 clinical medicine Endocrinology retinol binding protein lipid transport CRBP2 cellular retinol binding protein 2 Chemistry GIP gastric inhibitory polypeptide computer.file_format 2-LaG 2-lauroyl-glycerol monoacylglycerols high-throughput screening of lipids 1-AG 1-arachidonoylglycerol lipids (amino acids peptides and proteins) Plant lipid transfer proteins 3-ASG arachidonoyl-3-thioglycerol Research Article retinoids 2-PG 2-palmitoyl glycerol QD415-436 lipid transfer proteins 03 medical and health sciences atROL all-trans-retinol 2-AG 2-arachidonoylglycerol PDB Protein Data Bank All trans retinol Lipid Transport FABP1 fatty acid binding protein 1 Rbp2 2-LG 2-linoleoyl glycerol Lipid metabolism Retinol-Binding Proteins Cellular Cell Biology Protein Data Bank MAGs monoacylglycerols 3-AG 3-arachidonoylglycerol Retinol binding protein 030104 developmental biology computer 2-OG 2-oleoyl glycerol |
| Zdroj: | Journal of Lipid Research Journal of Lipid Research, Vol 62, Iss, Pp 100054-(2021) |
| ISSN: | 1539-7262 0022-2275 |
| Popis: | Present in the small intestine, cellular retinol binding protein 2 (CRBP2) plays an important role in the uptake, transport, and metabolism of dietary retinoids. However, the recent discovery of the interactions of CRBP2 with 2-arachidonoylglycerol and other monoacylglycerols (MAGs) suggests the broader involvement of this protein in lipid metabolism and signaling. To better understand the physiological role of CRBP2, we determined its protein-lipid interactome using a fluorescence-based retinol replacement assay adapted for a high-throughput screening format. By examining chemical libraries of bioactive lipids, we provided evidence for the selective interaction of CRBP2 with a subset of nonretinoid ligands with the highest affinity for sn-1 and sn-2 MAGs that contain polyunsaturated C18-C20 acyl chains. We also elucidated the structure-affinity relationship for nonretinoid ligands of this protein. We further dissect the molecular basis for this ligand's specificity by analyzing high-resolution crystal structures of CRBP2 in complex with selected derivatives of MAGs. Finally, we identify T51 and V62 as key amino acids that enable the broadening of ligand selectivity to MAGs in CRBP2 as compared with retinoid-specific CRBP1. Thus, our study provides the molecular framework for understanding the lipid selectivity and diverse functions of CRBPs in controlling lipid homeostasis. |
| Databáze: | OpenAIRE |
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