在内体pH值下LDL受体细胞外域的结构
Gabby Rudenko1, Lisa Henry, Keith Henderson
1Department of Biochemistry, University of Texas Southwestern Medical Center, 5323 Harry Hines Boulevard Y4-206, Dallas, TX 75390, USA.
概括
低密度脂蛋白受体释放的胆固醇在内分泌体. 一个拟议的机制涉及β螺旋域作为替代基质,促进胆固醇平衡的依赖的脂蛋白释放.
科学领域:
- 生物化学 生物化学
- 分子生物学分子生物学
- 细胞生物学 细胞生物学
背景情况:
- 低密度脂蛋白受体 (LDLR) 对于胆固醇平衡至关重要.
- LDLR 在酸性内分泌体中调解脂蛋白内分泌和配体释放.
- 了解连接体释放的结构基础是胆固醇代谢的关键.
研究的目的:
- 阐明内体中从LDLR释放脂蛋白的结构机制.
- 为了研究低pH的LDLR结构的作用.
主要方法:
- 在pH值5.3的X射线晶体学.
- 对LDLR连体结合和EGF前体同质域的结构分析.
主要成果:
- 在pH值为5.3时,LDLR连体结合域 (模块R2-R7) 在EGF前体同质域 (模块A,B,β螺旋,C) 上面弧形.
- R4和R5模块对于脂蛋白结合至关重要,通过它们的结合循环与β螺旋相互作用.
- 晶体结构揭示了一个特定的域相互作用在内体的pH.
结论:
- 提出了一种新的脂蛋白释放机制,涉及β螺旋领域.
- β螺旋以依赖的方式作为连接体结合域的替代基质.
- 这种相互作用促进脂蛋白释放,有助于胆固醇恒常.
相关概念视频
Receptor-mediated Endocytosis
Overview
Receptor-mediated Endocytosis
Receptor-mediated endocytosis is when bulk amounts of specific molecules are imported into a cell after binding to cell surface receptors. The molecules bound to these receptors are taken into the cell through inward folding of the cell surface membrane, which is eventually pinched off into a vesicle within the cell. Structural proteins, such as clathrin, coat the budding vesicle.
Clathrin-Mediated Endocytosis of LDL
One well-characterized example of receptor-mediated endocytosis is the...
Clathrin-Mediated Endocytosis of LDL
One well-characterized example of receptor-mediated endocytosis is the...
The Early Endosome: Endocytosis of Transferrin
Essential proteins such as insulin or low-density lipoprotein (LDL) and micronutrients such as iron enter a eukaryotic cell through receptor-mediated endocytosis. Subsequently, the early endosomes fuse with the vesicles containing such receptor-ligand complexes and play a vital role in sorting the incoming ligands and receptors. While the ligands are either degraded inside the vesicle or released into the cytosol, their receptors are returned to the plasma membrane for further rounds of...
Receptor Downregulation in MVBs
Multivesicular bodies (MVBs) are mature endosomes that sort ubiquitinated proteins and then fuse with lysosomes to degrade the sorted proteins. Epidermal growth factor (EGF) and its receptor (EGFR) form a complex that can be internalized through endocytosis, sorted into an MVB, and later degraded.
The EGFR can initiate signaling pathways that lead to cell proliferation, migration, and differentiation. Overexpression of EGFR stimulates cells to proliferate. Excessive EGFR activation may...
The EGFR can initiate signaling pathways that lead to cell proliferation, migration, and differentiation. Overexpression of EGFR stimulates cells to proliferate. Excessive EGFR activation may...
Clathrin Coated Vesicles
Clathrin-coated vesicles use endocytosis to transport receptors and lysosomal hydrolases from the Golgi to the lysosome in the late secretory pathway. Clathrin-mediated endocytosis was the first described endocytic process, and Clathrin-coated vesicles remain one of the most well-studied transport vesicles. The molecular machinery that generates clathrin-coated vesicles comprises over 50 proteins that precisely coordinate vesicle formation. Cell surface receptors concentrated in indented sites...
Receptor-Mediated Endocytosis
Receptor-mediated endocytosis is when bulk amounts of specific molecules are imported into a cell after binding to cell surface receptors. The molecules bound to these receptors are taken into the cell through inward folding of the cell surface membrane, which is eventually pinched off into a vesicle within the cell. Structural proteins, such as clathrin, coat the budding vesicle.
Clathrin-Mediated Endocytosis of LDL
One well-characterized example of receptor-mediated endocytosis is the...
Clathrin-Mediated Endocytosis of LDL
One well-characterized example of receptor-mediated endocytosis is the...


