RAS家族的小鸟苷三磷酸酶(GTP酶)是受到严格调控的信号分子,其功能进一步受到泛素化和蛋白水解作用的调节。亮氨酸拉链样转录调节因子1(LZTR1)作为Cullin-3 RING E3泛素连接酶的底物适配分子,能够结合特定的RAS GTP酶并促进其泛素化和...RAS家族的小鸟苷三磷酸酶(GTP酶)是受到严格调控的信号分子,其功能进一步受到泛素化和蛋白水解作用的调节。亮氨酸拉链样转录调节因子1(LZTR1)作为Cullin-3 RING E3泛素连接酶的底物适配分子,能够结合特定的RAS GTP酶并促进其泛素化和蛋白酶体降解。本研究展示了与RIT1、MRAS和KRAS结合的LZTR1Kelch结构域的结构,揭示了控制RAS亚型选择性和核苷酸特异性的相互作用界面。对疾病相关的Kelch结构域突变的生化和结构分析揭示了3种改变类型:底物相互作用受损、环区稳定性降低以及结构片层间排斥作用增强。在细胞和小鼠模型中,破坏底物结合的突变再现了LZTR1缺失的表型,突显了其底物特异性。这些发现明确了LZTR1识别RAS的机制,并提出了一种降解致癌性KRAS的“分子胶”策略。展开更多
How the tubular network of the endoplasmic reticulum (ER) is generated is not well understood, but a class of membrane proteins, the reticulons and DP1/Yop1p, are known
Understanding fundamental mechanisms governing axon outgrowth and guidance can inform the development of therapeutic strategies to restore neuronal function damaged though injury or disease. Axons navigate the extrace...Understanding fundamental mechanisms governing axon outgrowth and guidance can inform the development of therapeutic strategies to restore neuronal function damaged though injury or disease. Axons navigate the extracellular environment by responding to guidance cues that bind to cell surface receptors to relay information intracellularly via Rho GTPase family members, including the Rac GTPases.展开更多
Antigen cross-presentation in dendritic cells is a complex intracellular membrane transport process, but the underlying molecular mechanisms remain to be thoroughly investigated.
文摘RAS家族的小鸟苷三磷酸酶(GTP酶)是受到严格调控的信号分子,其功能进一步受到泛素化和蛋白水解作用的调节。亮氨酸拉链样转录调节因子1(LZTR1)作为Cullin-3 RING E3泛素连接酶的底物适配分子,能够结合特定的RAS GTP酶并促进其泛素化和蛋白酶体降解。本研究展示了与RIT1、MRAS和KRAS结合的LZTR1Kelch结构域的结构,揭示了控制RAS亚型选择性和核苷酸特异性的相互作用界面。对疾病相关的Kelch结构域突变的生化和结构分析揭示了3种改变类型:底物相互作用受损、环区稳定性降低以及结构片层间排斥作用增强。在细胞和小鼠模型中,破坏底物结合的突变再现了LZTR1缺失的表型,突显了其底物特异性。这些发现明确了LZTR1识别RAS的机制,并提出了一种降解致癌性KRAS的“分子胶”策略。
文摘How the tubular network of the endoplasmic reticulum (ER) is generated is not well understood, but a class of membrane proteins, the reticulons and DP1/Yop1p, are known
基金supported by a grant from an NHMRC Project Grant(GNT1105374)NHMRC Senior Research Fellowship(GNT1137645)a Victorian Endowment for Science,Knowledge and Innovation Fellowship(VIF23)(to RP)
文摘Understanding fundamental mechanisms governing axon outgrowth and guidance can inform the development of therapeutic strategies to restore neuronal function damaged though injury or disease. Axons navigate the extracellular environment by responding to guidance cues that bind to cell surface receptors to relay information intracellularly via Rho GTPase family members, including the Rac GTPases.
文摘Antigen cross-presentation in dendritic cells is a complex intracellular membrane transport process, but the underlying molecular mechanisms remain to be thoroughly investigated.
