Structure of the STRA6 receptor for retinol uptake.

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TitleStructure of the STRA6 receptor for retinol uptake.
Publication TypeJournal Article
Year of Publication2016
AuthorsChen, Y, Clarke, OB, Kim, J, Stowe, S, Kim, Y-K, Assur, Z, Cavalier, M, Godoy-Ruiz, R, von Alpen, DC, Manzini, C, Blaner, WS, Frank, J, Quadro, L, Weber, DJ, Shapiro, L, Hendrickson, WA, Mancia, F
JournalScience
Volume353
Issue6302
Date Published2016 08 26
ISSN1095-9203
KeywordsAnimals, Biological Transport, Calcium, Calmodulin, Cryoelectron Microscopy, HEK293 Cells, Humans, Membrane Proteins, Membrane Transport Proteins, Protein Binding, Protein Conformation, alpha-Helical, Protein Multimerization, Recombinant Proteins, Retinol-Binding Proteins, Vitamin A, Zebrafish Proteins
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.

DOI10.1126/science.aad8266
Alternate JournalScience
PubMed ID27563101
PubMed Central IDPMC5114850
Grant ListT32 HL120826 / HL / NHLBI NIH HHS / United States
R01 GM029169 / GM / NIGMS NIH HHS / United States
R01 DK101251 / DK / NIDDK NIH HHS / United States
R01 GM097089 / GM / NIGMS NIH HHS / United States
T32 AR007592 / AR / NIAMS NIH HHS / United States
P41 GM116799 / GM / NIGMS NIH HHS / United States
R01 GM111980 / GM / NIGMS NIH HHS / United States
U54 GM095315 / GM / NIGMS NIH HHS / United States
R01 HD083331 / HD / NICHD NIH HHS / United States
U54 GM075026 / GM / NIGMS NIH HHS / United States
R01 DK068437 / DK / NIDDK NIH HHS / United States
T32 CA154274 / CA / NCI NIH HHS / United States
R01 EY027405 / EY / NEI NIH HHS / United States