Structure of the STRA6 receptor for retinol uptake

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 recogni...

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Bibliographic Details
Published in:Science (American Association for the Advancement of Science) 2016-08, Vol.353 (6302), p.887-887
Main Authors: Chen, Yunting, Clarke, Oliver B., Kim, Jonathan, Stowe, Sean, Kim, Youn-Kyung, Assur, Zahra, Cavalier, Michael, Godoy-Ruiz, Raquel, von Alpen, Desiree C., Manzini, Chiara, Blaner, William S., Frank, Joachim, Quadro, Loredana, Weber, David J., Shapiro, Lawrence, Hendrickson, Wayne A., Mancia, Filippo
Format: Article
Language:English
Subjects:
Animals
Binding
Binding sites
Biological Transport
Calcium - chemistry
Calmodulin - chemistry
Cryoelectron Microscopy
Crystallography
Danio rerio
HEK293 Cells
Humans
Membrane Proteins - chemistry
Membrane Proteins - genetics
Membrane Transport Proteins - chemistry
Membrane Transport Proteins - genetics
Membranes
Metabolites
Microscopy
Nutrients
Peptides
Protein Binding
Protein Conformation, alpha-Helical
Protein Multimerization
Proteins
Receptors
Recombinant Proteins - chemistry
Recombinant Proteins - genetics
RESEARCH ARTICLE SUMMARY
Retinol-Binding Proteins - chemistry
Retinol-Binding Proteins - genetics
Topology
Uptakes
Vitamin A
Vitamin A - metabolism
Vitamins
Zebrafish
Zebrafish Proteins - chemistry
Zebrafish Proteins - genetics
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Summary: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.
ISSN:0036-8075
1095-9203
DOI:10.1126/science.aad8266