Structure of the STRA6 receptor for retinol uptake

被引：102

作者：

Chen, Yunting ^{[1
]}

Clarke, Oliver B. ^{[2
]}

Kim, Jonathan ^{[1
]}

Stowe, Sean ^{[3
,4
]}

Kim, Youn-Kyung ^{[5
,6
]}

Assur, Zahra ^{[1
]}

Cavalier, Michael ^{[3
,4
]}

Godoy-Ruiz, Raquel ^{[3
,4
]}

von Alpen, Desiree C. ^{[7
,8
]}

Manzini, Chiara ^{[7
,8
]}

Blaner, William S. ^{[9
]}

Frank, Joachim ^{[2
]}

Quadro, Loredana ^{[5
,6
]}

Weber, David J. ^{[3
,4
]}

Shapiro, Lawrence ^{[2
]}

Hendrickson, Wayne A. ^{[1
,2
]}

Mancia, Filippo ^{[1
]}

机构：

[1] Columbia Univ, Dept Physiol & Cellular Biophys, New York, NY 10032 USA

[2] Columbia Univ, Dept Biochem & Mol Biophys, 630 W 168th St, New York, NY 10032 USA

[3] Univ Maryland, Sch Med, Ctr Biomol Therapeut, Baltimore, MD 21201 USA

[4] Univ Maryland, Sch Med, Dept Biochem & Mol Biol, Baltimore, MD 21201 USA

[5] Rutgers State Univ, Dept Food Sci, New Brunswick, NJ 08901 USA

[6] Rutgers State Univ, Rutgers Ctr Lipid Res, New Brunswick, NJ 08901 USA

[7] George Washington Univ, Dept Physiol & Pharmacol, Washington, DC 20037 USA

[8] George Washington Univ, Dept Integrat Syst Biol, Washington, DC 20037 USA

[9] Columbia Univ, Dept Med, New York, NY 10032 USA

来源：

SCIENCE | 2016年 / 353卷 / 6302期

关键词：

BINDING-PROTEIN-RECEPTOR; MULTIPLE SEQUENCE ALIGNMENT; VITAMIN-A TRANSPORT; MEMBRANE-RECEPTOR; CELLULAR UPTAKE; WEB SERVER; HOLO-RBP; APO-RBP; ACTIVATION; CALMODULIN;

D O I：

10.1126/science.aad8266

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

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.

引用

页数：12

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