PUBLICATION
Structure of the STRA6 receptor for retinol uptake
- Authors
- Chen, Y., Clarke, O.B., Kim, J., Stowe, S., Kim, Y.K., Assur, Z., Cavalier, M., Godoy-Ruiz, R., von Alpen, D.C., Manzini, C., Blaner, W.S., Frank, J., Quadro, L., Weber, D.J., Shapiro, L., Hendrickson, W.A., Mancia, F.
- ID
- ZDB-PUB-160827-3
- Date
- 2016
- Source
- Science (New York, N.Y.) 353(6302): (Journal)
- Registered Authors
- Keywords
- none
- MeSH Terms
-
- Animals
- Membrane Proteins/chemistry*
- Membrane Proteins/genetics
- Zebrafish Proteins/chemistry*
- Zebrafish Proteins/genetics
- Calmodulin/chemistry
- Calcium/chemistry
- Protein Multimerization
- Protein Conformation, alpha-Helical
- Protein Binding
- Vitamin A/metabolism*
- Cryoelectron Microscopy
- HEK293 Cells
- Biological Transport
- Recombinant Proteins/chemistry
- Recombinant Proteins/genetics
- Retinol-Binding Proteins/chemistry*
- Retinol-Binding Proteins/genetics
- Membrane Transport Proteins/chemistry*
- Membrane Transport Proteins/genetics
- Humans
- PubMed
- 27563101 Full text @ Science
Citation
Chen, Y., Clarke, O.B., Kim, J., Stowe, S., Kim, Y.K., Assur, Z., Cavalier, M., Godoy-Ruiz, R., von Alpen, D.C., Manzini, C., Blaner, W.S., Frank, J., Quadro, L., Weber, D.J., Shapiro, L., Hendrickson, W.A., Mancia, F. (2016) Structure of the STRA6 receptor for retinol uptake. Science (New York, N.Y.). 353(6302).
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.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping