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Science. 2016 Aug 26;353(6302). pii: aad8266. doi: 10.1126/science.aad8266.

Structure of the STRA6 receptor for retinol uptake.

Author information

1
Department of Physiology and Cellular Biophysics, Columbia University, New York, NY 10032, USA.
2
Department of Biochemistry and Molecular Biophysics, Columbia University, New York, NY 10032, USA.
3
The Center for Biomolecular Therapeutics and Department of Biochemistry and Molecular Biology, University of Maryland School of Medicine, Baltimore, MD 21201, USA.
4
Department of Food Science and Rutgers Center for Lipid Research, Rutgers University, New Brunswick, NJ 08901, USA.
5
Department of Pharmacology and Physiology and Department of Integrative Systems Biology, George Washington University, Washington, DC 20037, USA.
6
Department of Medicine, Columbia University, New York, NY 10032, USA.
7
Department of Physiology and Cellular Biophysics, Columbia University, New York, NY 10032, USA. Department of Biochemistry and Molecular Biophysics, Columbia University, New York, NY 10032, USA.
8
Department of Physiology and Cellular Biophysics, Columbia University, New York, NY 10032, USA. fm123@cumc.columbia.edu.

Abstract

Vitamin A homeostasis is critical to normal cellular function. Retinol-binding protein (RBP) is the sole specific carrier in the bloodstream for hydrophobic retinol, the main form in which vitamin A is transported. The integral membrane receptor STRA6 mediates cellular uptake of vitamin A by recognizing RBP-retinol to trigger release and internalization of retinol. We present the structure of zebrafish STRA6 determined to 3.9-angstrom resolution by single-particle cryo-electron microscopy. STRA6 has one intramembrane and nine transmembrane helices in an intricate dimeric assembly. Unexpectedly, calmodulin is bound tightly to STRA6 in a noncanonical arrangement. Residues involved with RBP binding map to an archlike structure that covers a deep lipophilic cleft. This cleft is open to the membrane, suggesting a possible mode for internalization of retinol through direct diffusion into the lipid bilayer.

PMID:
27563101
PMCID:
PMC5114850
[Available on 2017-02-26]
DOI:
10.1126/science.aad8266
[Indexed for MEDLINE]
Free PMC Article

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