title: Structure of the STRA6 receptor for retinol uptake.
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.
authors: Department of Physiology and Cellular Biophysics, Columbia University, New York, NY 10032, USA.
authors: Yunting
authors: Y
authors: Chen
authors: Department of Biochemistry and Molecular Biophysics, Columbia University, New York, NY 10032, USA.
authors: Oliver B
authors: OB
authors: Clarke
authors: Department of Physiology and Cellular Biophysics, Columbia University, New York, NY 10032, USA.
authors: Jonathan
authors: J
authors: Kim
authors: The Center for Biomolecular Therapeutics and Department of Biochemistry and Molecular Biology, University of Maryland School of Medicine, Baltimore, MD 21201, USA.
authors: Sean
authors: S
authors: Stowe
authors: Department of Food Science and Rutgers Center for Lipid Research, Rutgers University, New Brunswick, NJ 08901, USA.
authors: Youn-Kyung
authors: YK
authors: Kim
authors: Department of Physiology and Cellular Biophysics, Columbia University, New York, NY 10032, USA.
authors: Zahra
authors: Z
authors: Assur
authors: The Center for Biomolecular Therapeutics and Department of Biochemistry and Molecular Biology, University of Maryland School of Medicine, Baltimore, MD 21201, USA.
authors: Michael
authors: M
authors: Cavalier
authors: The Center for Biomolecular Therapeutics and Department of Biochemistry and Molecular Biology, University of Maryland School of Medicine, Baltimore, MD 21201, USA.
authors: Raquel
authors: R
authors: Godoy-Ruiz
authors: Department of Pharmacology and Physiology and Department of Integrative Systems Biology, George Washington University, Washington, DC 20037, USA.
authors: Desiree C
authors: DC
authors: von Alpen
authors: Department of Pharmacology and Physiology and Department of Integrative Systems Biology, George Washington University, Washington, DC 20037, USA.
authors: Chiara
authors: C
authors: Manzini
authors: Department of Medicine, Columbia University, New York, NY 10032, USA.
authors: William S
authors: WS
authors: Blaner
authors: Department of Biochemistry and Molecular Biophysics, Columbia University, New York, NY 10032, USA.
authors: Joachim
authors: J
authors: Frank
authors: Department of Food Science and Rutgers Center for Lipid Research, Rutgers University, New Brunswick, NJ 08901, USA.
authors: Loredana
authors: L
authors: Quadro
authors: The Center for Biomolecular Therapeutics and Department of Biochemistry and Molecular Biology, University of Maryland School of Medicine, Baltimore, MD 21201, USA.
authors: David J
authors: DJ
authors: Weber
authors: Department of Biochemistry and Molecular Biophysics, Columbia University, New York, NY 10032, USA.
authors: Lawrence
authors: L
authors: Shapiro
authors: 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.
authors: Wayne A
authors: WA
authors: Hendrickson
authors: Department of Physiology and Cellular Biophysics, Columbia University, New York, NY 10032, USA. fm123@cumc.columbia.edu.
authors: Filippo
authors: F
authors: Mancia
mesh_terms: D000818:Animals; D001692:Biological Transport; D002118:Calcium / Q000737:chemistry; D002147:Calmodulin / Q000737:chemistry; D020285:Cryoelectron Microscopy; D057809:HEK293 Cells; D006801:Humans; D008565:Membrane Proteins / Q000737:chemistry* / Q000235:genetics; D026901:Membrane Transport Proteins / Q000737:chemistry* / Q000235:genetics; D011485:Protein Binding; D000072756:Protein Conformation, alpha-Helical; D055503:Protein Multimerization; D011994:Recombinant Proteins / Q000737:chemistry / Q000235:genetics; D012177:Retinol-Binding Proteins / Q000737:chemistry* / Q000235:genetics; D014801:Vitamin A / Q000378:metabolism*; D029961:Zebrafish Proteins / Q000737:chemistry* / Q000235:genetics
chemical_list: D002147:Calmodulin; D008565:Membrane Proteins; D026901:Membrane Transport Proteins; D011994:Recombinant Proteins; D012177:Retinol-Binding Proteins; C000614448:STRA6 protein, zebrafish; D029961:Zebrafish Proteins; D014801:Vitamin A; D002118:Calcium