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
  • Biological Transport
  • Calcium/chemistry
  • Calmodulin/chemistry
  • Cryoelectron Microscopy
  • HEK293 Cells
  • Humans
  • Membrane Proteins/chemistry*
  • Membrane Proteins/genetics
  • Membrane Transport Proteins/chemistry*
  • Membrane Transport Proteins/genetics
  • Protein Binding
  • Protein Conformation, alpha-Helical
  • Protein Multimerization
  • Recombinant Proteins/chemistry
  • Recombinant Proteins/genetics
  • Retinol-Binding Proteins/chemistry*
  • Retinol-Binding Proteins/genetics
  • Vitamin A/metabolism*
  • Zebrafish Proteins/chemistry*
  • Zebrafish Proteins/genetics
PubMed
27563101 Full text @ Science
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
Figures
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Antibodies
Orthology
Engineered Foreign Genes
Mapping