Structural basis of receptor-mediated cellular vitamin A uptake

受体介导的细胞维生素 A 摄取的结构基础

基本信息

  • 批准号:
    9898381
  • 负责人:
  • 金额:
    $ 49.82万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
  • 财政年份:
    2017
  • 资助国家:
    美国
  • 起止时间:
    2017-04-01 至 2022-03-31
  • 项目状态:
    已结题

项目摘要

Vitamin A is an essential nutrient for all mammals. Many biological processes, including and foremost vision, are crucially dependent on its adequate supply for proper function. Alterations of vitamin A metabolism can result in a wide spectrum of ocular defects and lead to blindness. Retinol (vitamin A alcohol) is the predominant circulating vitamin A form in the fasting state. In times of need (i.e. in the absence of dietary vitamin A intake), in order to distribute vitamin A to the target peripheral tissues, retinol is released in the bloodstream from the liver, the main body storage site of the vitamin, bound to retinol-binding protein (RBP). Inside the cells, retinol binds specific intracellular carriers, namely cellular retinol-binding proteins, and it serves as a precursor for the active vitamin A forms: retinaldehyde, critical for vision, and retinoic acid, the ligand for specific nuclear receptors that regulate the transcription of hundreds of target genes. How retinol is released from the retinol-RBP complex and internalized by the cell has been subject of debate for decades. STRA6, the putative plasma membrane receptor for RBP, was identified in 2007. However, its mechanism of action has remained elusive, not least due to the absence of any structural information. Here we present the structure of STRA6 determined to 4.2 Å resolution by single-particle cryo-electron microscopy. STRA6 is a dimer, with each protomer contributing nine transmembrane and a horizontal intramembrane helix that is positioned at the core of the dimer interface. Unexpectedly, the C-terminus of each protomer is tightly bound to calmodulin in a compact, non-canonical arrangement. The structure suggests possible sites for interaction with extracellular and intracellular carriers for retinol, and modes for internalization of retinol. The atomic model of STRA6 provides a template to guide our understanding at a molecular level on how this protein may function, and to further investigate its physiological role.
维生素A是所有哺乳动物必需的营养素。许多生物过程,包括最重要的视觉,都至关重要地依赖于它的充足供应来维持正常功能。维生素A代谢的改变可导致广泛的眼部缺陷并导致失明。

项目成果

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Filippo Mancia其他文献

Filippo Mancia的其他文献

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{{ truncateString('Filippo Mancia', 18)}}的其他基金

Molecular Mechanisms of Wnt Transport
Wnt 转运的分子机制
  • 批准号:
    10753139
  • 财政年份:
    2023
  • 资助金额:
    $ 49.82万
  • 项目类别:
Molecular mechanism of omega-3 fatty acid transport into the brain
omega-3脂肪酸转运至大脑的分子机制
  • 批准号:
    10307571
  • 财政年份:
    2020
  • 资助金额:
    $ 49.82万
  • 项目类别:
Molecular mechanism of omega-3 fatty acid transport into the brain
omega-3脂肪酸转运至大脑的分子机制
  • 批准号:
    10156975
  • 财政年份:
    2020
  • 资助金额:
    $ 49.82万
  • 项目类别:
Structural basis of integral membrane enzyme function
完整膜酶功能的结构基础
  • 批准号:
    10609459
  • 财政年份:
    2019
  • 资助金额:
    $ 49.82万
  • 项目类别:
Structural basis of integral membrane enzyme function
完整膜酶功能的结构基础
  • 批准号:
    9921455
  • 财政年份:
    2019
  • 资助金额:
    $ 49.82万
  • 项目类别:
Structural basis of integral membrane enzyme function
完整膜酶功能的结构基础
  • 批准号:
    10582102
  • 财政年份:
    2019
  • 资助金额:
    $ 49.82万
  • 项目类别:
Structural basis of integral membrane enzyme function
完整膜酶功能的结构基础
  • 批准号:
    10393522
  • 财政年份:
    2019
  • 资助金额:
    $ 49.82万
  • 项目类别:
Structural basis of phosphoinositide biosynthesis in Mycobacterium tuberculosis
结核分枝杆菌中磷酸肌醇生物合成的结构基础
  • 批准号:
    9100634
  • 财政年份:
    2015
  • 资助金额:
    $ 49.82万
  • 项目类别:
Structural basis of phosphoinositide biosynthesis in Mycobacterium tuberculosis
结核分枝杆菌中磷酸肌醇生物合成的结构基础
  • 批准号:
    8953854
  • 财政年份:
    2015
  • 资助金额:
    $ 49.82万
  • 项目类别:
CysZ proteins_A family of sulfate transporters with remarkable architecture
CysZ蛋白_具有卓越结构的硫酸盐转运蛋白家族
  • 批准号:
    8461956
  • 财政年份:
    2012
  • 资助金额:
    $ 49.82万
  • 项目类别:

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  • 批准号:
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