GTP binding controls complex formation by the human ROCO protein MASL1.
GTP binding controls complex formation by the human ROCO protein MASL1.
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DOI：
10.1111/febs.12593
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发表时间：
2014-01
期刊：
影响因子：
--
通讯作者：
Lewis PA
中科院分区：
文献类型：
--
作者：
Dihanich S;Civiero L;Manzoni C;Mamais A;Bandopadhyay R;Greggio E;Lewis PA
人ROCO蛋白是一个多结构域蛋白家族，具有一个保守的ROC-COR超结构域。该家族有四个成员：富亮氨酸重复蛋白1(LRRK1)、富亮氨酸重复蛋白2(LRRK2)、死亡相关蛋白激酶1(DAPK1)和恶性纤维组织细胞瘤扩增序列富亮氨酸串联重复序列1(MASL1)。以前对LRRK1/2和DAPK1的研究表明，ROC(Ras Of Complex Proteins)结构域可以结合和水解GTP，但这种活性的细胞后果尚不清楚。在这里，首次报道了MASL1的生化特征以及GTP结合对MASL1复合体形成的影响。结果表明，MASL1与其他ROCO蛋白一样，可以通过其ROC结构域与鸟苷核苷酸结合。此外，MASL1存在于与热休克蛋白60相关的两个不同的细胞复合体中，MASL1低分子量池的形成受GTP结合的调控。最后，GTP的丢失增强了MASL1在细胞中的毒性。综上所述，这些数据表明MASL1的ROC/GTPase结构域在其细胞功能调节中发挥着核心作用。HSP60和MASL1通过分子筛选相互作用(View Interaction)MASL1通过反标签免疫共沉淀与HSP70和HSP60物理相互作用(View Interaction)MASL1通过反标签免疫共沉淀与HSP60物理相互作用(View Interaction)
The human ROCO proteins are a family of multi-domain proteins sharing a conserved ROC-COR supra-domain. The family has four members: leucine-rich repeat kinase 1 (LRRK1), leucine-rich repeat kinase 2 (LRRK2), death-associated protein kinase 1 (DAPK1) and malignant fibrous histiocytoma amplified sequences with leucine-rich tandem repeats 1 (MASL1). Previous studies of LRRK1/2 and DAPK1 have shown that the ROC (Ras of complex proteins) domain can bind and hydrolyse GTP, but the cellular consequences of this activity are still unclear. Here, the first biochemical characterization of MASL1 and the impact of GTP binding on MASL1 complex formation are reported. The results demonstrate that MASL1, similar to other ROCO proteins, can bind guanosine nucleotides via its ROC domain. Furthermore, MASL1 exists in two distinct cellular complexes associated with heat shock protein 60, and the formation of a low molecular weight pool of MASL1 is modulated by GTP binding. Finally, loss of GTP enhances MASL1 toxicity in cells. Taken together, these data point to a central role for the ROC/GTPase domain of MASL1 in the regulation of its cellular function. HSP60 and MASL1 physically interact by molecular sieving (View interaction) MASL1 physically interacts with HSP70 and HSP60 by anti tag coimmunoprecipitation (View interaction) MASL1 physically interacts with HSP60 by anti tag coimmunoprecipitation (View interaction)
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DOI：
10.1523/jneurosci.5601-11.2012
发表时间：
2012-02-01
期刊：
The Journal of neuroscience : the official journal of the Society for Neuroscience
影响因子：
--
作者：
Moehle MS;Webber PJ;Tse T;Sukar N;Standaert DG;DeSilva TM;Cowell RM;West AB
通讯作者：
West AB
DOI：
10.1073/pnas.1000093107
发表时间：
2011-03-15
影响因子：
11.1
作者：
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通讯作者：
Xavier, Ramnik J.
影响因子：
11.2
作者：
Biskup, Saskia;Moore, Darren J.;Dawson, Valina L.
通讯作者：
Dawson, Valina L.
影响因子：
4.8
作者：
Greggio, Elisa;Zambrano, Ibardo;Cookson, Mark R.
通讯作者：
Cookson, Mark R.
影响因子：
4.8
作者：
Korr, D;Toschi, L;Weiss, B
通讯作者：
Weiss, B