[Seminar] The Molecular Mechanisms Underlying Cellular Uptake of Vitamin A

Seminar

Title: The Molecular Mechanisms Underlying Cellular Uptake of Vitamin A

Speaker: Filippo Mancia

Affiliation: Associate Professor of Physiology & Cellular Biophysics, Structural biology of integral membrane proteins, Columbia University Medical Center, New York​ (His main research focus is on membrane protein – lipid interactions.)

Host: Helena Santos Lab - Cell Physiology and NMR

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.

A few recent publications of Dr. Mancia

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. and Mancia, F. (2016). Structure of the STRA6 receptor for retinol uptake. Science, 353, pii: aad8266. doi: 10.1126/science.aad8266.

Petrou, V.I., Herrera, C.M., Schultz, K.M., Clarke, O.B., Vendome, J., Tomasek, D., Banerjee, S., Rajashankar, K.R., Belcher Dufrisne, M., Kloss, B., Kloppmann, E., Rost, B., Klug, C.S., Trent, M.S., Shapiro, L. and Mancia, F. (2016). Structures of aminoarabinose transferase ArnT suggest a molecular basis for resistance to polymyxins. Science, 351, 608-612.

Ardiccioni, C., Clarke, O.B., Tomasek, D., Issa, H.A., von Alpen, D.C., Pond, H.L., Banerjee, S., Rajashankar, K.R., Liu, Q., Guan, Z., Li, C., Kloss, B., Bruni, R., Kloppmann, E., Rost, B., Manzini, M.C., Shapiro, L. and Mancia, F. (2016). Structure of the polyisoprenyl-phosphate glycosyltransferase GtrB and insights into the mechanism of catalysis. Nat. Commun., 7:10175. doi: 10.1038/ncomms10175.

Clarke, O.B., Tomasek, D., Jorge, C.D., Belcher Dufrisne, M., Kim, M., Banerjee, S., Rajashankar, K.R., Shapiro, L., Hendrickson, W.A., Santos, H. and Mancia, F. (2015). Structural basis for phosphatidylinositol-phosphate biosynthesis. Nat. Commun., 6:8505. doi: 10.1038/ncomms9505.