6bth
Crystal structure of human cellular retinol binding protein 2 (CRBP2) in complex with 2-arachidonoylglycerol (2-AG)Crystal structure of human cellular retinol binding protein 2 (CRBP2) in complex with 2-arachidonoylglycerol (2-AG)
Structural highlights
FunctionRET2_HUMAN Intracellular transport of retinol. Publication Abstract from PubMedExpressed in the small intestine, retinol-binding protein 2 (RBP2) facilitates dietary retinoid absorption. Rbp2-deficient (Rbp2(-/-) ) 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 Rbp2(-/-) 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, Rbp2(-/-) 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. Retinol-binding protein 2 (RBP2) binds monoacylglycerols and modulates gut endocrine signaling and body weight.,Lee SA, Yang KJZ, Brun PJ, Silvaroli JA, Yuen JJ, Shmarakov I, Jiang H, Feranil JB, Li X, Lackey AI, Krezel W, Leibel RL, Libien J, Storch J, Golczak M, Blaner WS Sci Adv. 2020 Mar 11;6(11):eaay8937. doi: 10.1126/sciadv.aay8937. eCollection, 2020 Mar. PMID:32195347[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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