Structure of the STRA6 receptor for retinol uptake

Science. 2016 Aug 26;353(6302):aad8266. doi: 10.1126/science.aad8266.

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.

Publication types

  • Research Support, N.I.H., Extramural

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

Substances

  • Calmodulin
  • Membrane Proteins
  • Membrane Transport Proteins
  • Recombinant Proteins
  • Retinol-Binding Proteins
  • STRA6 protein, zebrafish
  • Zebrafish Proteins
  • Vitamin A
  • Calcium