6BTH
Crystal structure of human cellular retinol binding protein 2 (CRBP2) in complex with 2-arachidonoylglycerol (2-AG)
Summary for 6BTH
| Entry DOI | 10.2210/pdb6bth/pdb |
| Descriptor | Retinol-binding protein 2, 1,3-dihydroxypropan-2-yl (5Z,8Z,11Z,14Z)-icosa-5,8,11,14-tetraenoate, DI(HYDROXYETHYL)ETHER, ... (4 entities in total) |
| Functional Keywords | endocannabinoid, 2-arachidonoylglycerol, 2-ag, retinol, vitamin a, lipid binding protein |
| Biological source | Homo sapiens (Human) |
| Total number of polymer chains | 2 |
| Total formula weight | 33465.94 |
| Authors | Silvaroli, J.A.,Blaner, W.S.,Lodowski, D.T.,Golczak, M. (deposition date: 2017-12-06, release date: 2018-12-12, Last modification date: 2023-10-04) |
| Primary citation | Lee, S.A.,Yang, K.J.Z.,Brun, P.J.,Silvaroli, J.A.,Yuen, J.J.,Shmarakov, I.,Jiang, H.,Feranil, J.B.,Li, X.,Lackey, A.I.,Krezel, W.,Leibel, R.L.,Libien, J.,Storch, J.,Golczak, M.,Blaner, W.S. Retinol-binding protein 2 (RBP2) binds monoacylglycerols and modulates gut endocrine signaling and body weight. Sci Adv, 6:eaay8937-eaay8937, 2020 Cited by PubMed Abstract: Expressed in the small intestine, retinol-binding protein 2 (RBP2) facilitates dietary retinoid absorption. -deficient ( ) mice fed a chow diet exhibit by 6-7 months-of-age higher body weights, impaired glucose metabolism, and greater hepatic triglyceride levels compared to controls. These phenotypes are also observed when young mice are fed a high fat diet. Retinoids do not account for the phenotypes. Rather, RBP2 is a previously unidentified monoacylglycerol (MAG)-binding protein, interacting with the endocannabinoid 2-arachidonoylglycerol (2-AG) and other MAGs with affinities comparable to retinol. X-ray crystallographic studies show that MAGs bind in the retinol binding pocket. When challenged with an oil gavage, mice show elevated mucosal levels of 2-MAGs. This is accompanied by significantly elevated blood levels of the gut hormone GIP (glucose-dependent insulinotropic polypeptide). Thus, RBP2, in addition to facilitating dietary retinoid absorption, modulates MAG metabolism and likely signaling, playing a heretofore unknown role in systemic energy balance. PubMed: 32195347DOI: 10.1126/sciadv.aay8937 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (1.35 Å) |
Structure validation
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