检索结果-南通市图书馆

Arrestins:structural disorder creates rich functionality

Protein & Cell 2018年第12期9卷 986-1003页

作者： vsevolod v.gurevich Eugenia v.gurevich vladimir N.Uversky Department of Pharmacology Vanderbilt UniversityNashvilleTN 37232USA Department of Molecular Medicine and USF Health Byrd Alzheimer's Research Institute Morsani College of Medicine University of South FloridaTampaFL 33612USA Institute for Biological Instrumentation Russian Academy of SciencesPushchinoMoscow RegionRussia 142290

Arrestins are soluble relatively small 44-46 kDa proteins that specifically bind hundreds of active phosphorylated GPCRs and dozens of non-receptor partners. There are binding partners that demonstrate preference for each of the known arrestin conformations: free, receptor-bound, and microtubule-bound. Recent evidence suggests that conformational flexibility in every functional state is the defining characteristic of arrestins. Flexibility, or plasticity, of proteins is often described as structural disorder, in contrast to the fixed conformational order observed in high-resolution crystal structures. However, protein-protein interactions often involve highly flexible elements that can assume many distinct conformations upon binding to different partners. Existing evidence suggests that arrestins are no exception to this rule: their flexibility is necessary for functional versatility. The data on arrestins and many other multi-functional proteins indicate that in many cases, "order" might be artificially imposed by highly non-physiological crystallization conditions and/or crystal packing forces. In contrast, conformational flexibility (and its extreme case, intrinsic disorder) is a more natural state of proteins, representing true biological order that underlies their physiologically relevant functions.

关键词： EPR GPCR NMR arrestin crystal structure disorder protein-protein interactions

来源：

维普期刊数据库评论

在线全文

维普期刊数据库

学校读者我要写书评

暂无评论

How genetic errors in GPCRs affect their function:Possible therapeutic strategies

引用

Genes & Diseases 2015年第2期2卷 108-132页

作者： Henriette Stoy vsevolod v.gurevich University of Tu¨bingen Tu¨bingen 72074Germany Department of Pharmacology Vanderbilt UniversityNashvilleTN 37232USA

Activating and inactivating mutations in numerous human G protein-coupled receptors(GPCRs)are associated with a wide range of disease phenotypes.Here we use several class A GPCRs with a particularly large set of identified disease-associated mutations,many of which were biochemically characterized,along with known GPCR structures and current models of GPCR activation,to understand the molecular mechanisms yielding pathological phenotypes.Based on this mechanistic understanding we also propose different therapeutic approaches,both conventional,using small molecule ligands,and novel,involving gene therapy.

关键词： Activation Agonist Mutation Gene therapy Genetic disorder GPCR

来源：

维普期刊数据库评论

在线全文

维普期刊数据库

学校读者我要写书评

暂无评论

Arrestin-mediated signaling: Is there a controversy?

引用

World Journal of Biological Chemistry 2018年第3期9卷 25-35页

作者： vsevolod v.gurevich Eugenia v.gurevich Department of Pharmacology Vanderbilt University

The activation of the mitogen-activated protein(MAP) kinases extracellular signal-regulated kinase(ERK)1/2 was traditionally used as a readout of signaling of G protein-coupled receptors(GPCRs) via arrestins, as opposed to conventional GPCR signaling via G proteins. Several recent studies using HEK293 cells where all G proteins were genetically ablated or inactivated, or both non-visual arrestins were knocked out, demonstrated that ERK1/2 phosphorylation requires G protein activity, but does not necessarily require the presence of non-visual arrestins. This appears to contradict the prevailing paradigm. Here we discuss these results along with the recent data on gene edited cells and arrestinmediated signaling. We suggest that there is no real controversy. G proteins might be involved in the activation of the upstream-most MAP3Ks, although in vivo most MAP3K activation is independent of heterotrimeric G proteins, being initiated by receptor tyrosine kinases and/or integrins. As far as MAP kinases are concerned, the best-established role of arrestins is scaffolding of the three-tiered cascades(MAP3K-MAP2 K-MAPK). Thus, it seems likely that arrestins, GPCRbound and free, facilitate the propagation of signals in these cascades, whereas signal initiation via MAP3K activation may be independent of arrestins. Different MAP3Ks are activated by various inputs, some of which are mediated by G proteins, particularly in cell culture, where we artificially prevent signaling by receptor tyrosine kinases and integrins, thereby favoring GPCR-induced signaling. Thus, there is no reason to change the paradigm: Arrestins and G proteins play distinct non-overlapping roles in cell signaling.

关键词： G protein-coupled receptors Arrestin G protein Signaling Extracellular signal-regulated kinase 1/2 c-Jun N-terminal kinase 3

来源：

维普期刊数据库评论

在线全文

维普期刊数据库

学校读者我要写书评

暂无评论

L-Norvaline, a new therapeutic agent against Alzheimer’s disease

引用

Neural Regeneration Research 2019年第9期14卷 1562-1572页

作者： Baruh Polis Kolluru D.Srikanth vyacheslav.gurevich Hava Gil-Henn Abraham O.Samson Drug Discovery Laboratory The Azrieli Faculty of MedicineBar-Ilan UniversitySafedIsrael Laboratory of Cell Migration and Invasion The Azrieli Faculty of MedicineBar-Ilan UniversitySafedIsrael Laboratory of Cancer Personalized Medicine and Diagnostic Genomics The Azrieli Faculty of MedicineBar-Ilan UniversitySafedIsrael

Growing evidence highlights the role of arginase activity in the manifestation of Alzheimer’s disease(AD).Upregulation of arginase was shown to contribute to neurodegeneration.Regulation of arginase activity appears to be a promising approach for interfering with the pathogenesis of AD.Therefore,the enzyme represents a novel therapeutic target.In this study,we administered an arginase inhibitor,L-norvaline(250 mg/L),for 2.5 months to a triple-transgenic model(3×Tg-AD)harboring PS1M146v,APPSwe,and tauP301L transgenes.Then,the neuroprotective effects of L-norvaline were evaluated using immunohistochemistry,proteomics,and quantitative polymerase chain reaction assays.Finally,we identified the biological pathways activated by the treatment.Remarkably,L-norvaline treatment reverses the cognitive decline in AD mice.The treatment is neuroprotective as indicated by reduced beta-amyloidosis,alleviated microgliosis,and reduced tumor necrosis factor transcription levels.Moreover,elevated levels of neuroplasticity related postsynaptic density protein 95 were detected in the hippocampi of mice treated with L-norvaline.Furthermore,we disclosed several biological pathways,which were involved in cell survival and neuroplasticity and were activated by the treatment.Through these modes of action,L-norvaline has the potential to improve the symptoms of AD and even interferes with its pathogenesis.As such,L-norvaline is a promising neuroprotective molecule that might be tailored for the treatment of a range of neurodegenerative disorders.The study was approved by the Bar-Ilan University Animal Care and Use Committee(approval No.82-10-2017)on October 1,2017.

关键词： dementia arginase inhibition arginine urea cycle microgliosis neuroinflammation cytokines tumor necrosis factor mTOR neurodegeneration

来源：

维普期刊数据库

同方期刊数据库评论

在线全文

学校读者我要写书评

暂无评论

生物再生生命保障系统设计的基本问题

引用

航天医学与医学工程 2008年第4期21卷 372-376页

作者：刘红胡恩柱胡大伟 Manukovsky N.S. Kovalev v. S. gurevich Y. L. 北京航空航天大学生物与医学工程学院北京100083 Institute of Biophysics SB of RAS Krasnoyarsk660036 Russia

生物再生生命保障系统(BLSS)是建立月球/火星基地,实现中长期载人空间飞行必须解决的关键技术。利用高等植物或微藻来生产食物、处理废物、再生O2和水是BLSS区别于其他类型生保系统的重要标志。BLSS在结构和功能上可以分为自养单元和异... 详细信息

生物再生生命保障系统(BLSS)是建立月球/火星基地,实现中长期载人空间飞行必须解决的关键技术。利用高等植物或微藻来生产食物、处理废物、再生O2和水是BLSS区别于其他类型生保系统的重要标志。BLSS在结构和功能上可以分为自养单元和异养单元两部分。本文简单绘制了三种不同的系统构型。在实际选择时,应根据任务需求选择系统综合质量最小的构型而不是单纯追求高封闭度。系统设计过程应遵循物质平衡的基本原则,尤其是与航天员生命息息相关的O2平衡和水平衡。

关键词：生物再生生命保障系统封闭度物质平衡 O2平衡水平衡

来源：

维普期刊数据库

同方期刊数据库评论

在线全文

学校读者我要写书评

暂无评论

一种新工艺制备的类土壤基质的特性

一种新工艺制备的类土壤基质的特性

引用

中国空间科学学会第七次学术年会

作者：何文婷刑一东刘红谢倍珍 Manukovsky N.S. Kovalev v.S. gurevich Yu. 北京航空航天大学生物与医学工程学院俄罗斯科学院西伯利亚分院生物物理研究所

高等植物不可食部分的处理是提高生物再生生命保障系统闭合性的关键问题之一,类土壤基质技术是实现植物不可食部分系统内循环处理最有前景的方法,本文针对一种新工艺制备的类土壤基质进行研究。该制备工艺过程为:将粉碎后的秸秆经过60... 详细信息

高等植物不可食部分的处理是提高生物再生生命保障系统闭合性的关键问题之一,类土壤基质技术是实现植物不可食部分系统内循环处理最有前景的方法,本文针对一种新工艺制备的类土壤基质进行研究。该制备工艺过程为:将粉碎后的秸秆经过60℃恒温好氧发酵24h,随后45℃发酵好氧48h的预处理后、在蚯蚓和微生物的作用下连续处理3个月。该工艺制备周期为93天,比传统工艺减少30天,基质转化率达到30%,其纤维素与木质素降解率分别达到98.6%和93.12%,生菜生产力达到12.01g·m·d,比传统工艺提高33%。

关键词：类土壤基质再生生命保障系统植物不可食生物量

来源： cnki会议评论

在线全文

cnki会议

学校读者我要写书评

暂无评论

帕金森病、多系统萎缩和单纯自主神经衰竭患者的脑血管收缩反应

引用

世界核心医学期刊文摘(神经病学分册) 2006年第8期 29-30页

作者： gurevich T. Gur A.Y. Bornstein N.M 陈海 Movement Disorders Unit Neurology Department Tel- Aviv Sourasky Medical Center 6 Weizmann St. Tel- Aviv Israel

Parkinson’s disease (PD), multiple system atrophy (MSA) and pure autonomic failure (PAF) are neurodegenerative disorders frequently associated with orthostatic hypotension and syncope, though with different underlying mechanisms. Cerebral hemodynamic responses in these three neurodegenerative diseases are still incompletely studied and it is possible that they would be differentially affected. We measured blood flow velocity (BFv) in the middle cerebral artery (MCA) and vertebral artery (vA) in patients with these disorders and investigated whether cerebral vasomotor reactivity (vMR) differs in these three disorders. Twenty- four patients (9 with PD, 10 with MSA and 5 with PAF) were studied. vMR was assessed in the MCA and vA, using transcranial Doppler (TCD) and Diamox test (injection of 1 g acetazolamide i.v.) with the patients in a recumbent position. The percent difference between BFv before and after acetazolamide injection was defined as vMR% and the results were compared by ANOvA. The mean MCA and vA blood flow velocities were similar in the three disorders and within normal limits for our laboratory. The mean MCA vMR values were 37.5 ± 24.0% , 27.9 ± 28.0% and 38.0 ± 33.9% in PD, MSA and PAF, respectively. The vA vMR values were 22.9 ± 23.6% , 32.4 ± 38.0% and 18.9 ± 18.3% , respectively, with no significant differences between the groups. We conclude that BFvis normal in PD, MSA and PAF and that the vMR, as investigated by TCD and the Diamox test, did not disclose differences in cerebral vasomotor responses between these conditions.

关键词：帕金森病脑血管自主神经多系统萎缩脑病患者

来源：

同方期刊数据库评论

在线全文

同方期刊数据库

学校读者我要写书评

暂无评论

欢迎您,

建议与咨询留下您的常用邮箱和电话号码，以便我们向您反馈解决方案和替代方法

时间限定

文献类型

馆藏选择

核心期刊

语言

文献类型

帮助

文字说明：

检索规则说明：

检索范例：

分类表

所选分类

限定检索结果

文献类型

馆藏范围

日期分布

学科分类号

主题

机构

作者

语言

在线全文

在线全文

在线全文

在线全文

在线全文

在线全文

在线全文

请选择保存的检索档案：

请选择收藏分类：

通借通还

欢迎您,

建议与咨询 留下您的常用邮箱和电话号码，以便我们向您反馈解决方案和替代方法

时间限定

文献类型

馆藏选择

核心期刊

语言

文献类型

帮助

文字说明：

检索规则说明：

检索范例：

分类表

所选分类

限定检索结果

文献类型

馆藏范围

日期分布

学科分类号

主题

机构

作者

语言

在线全文

在线全文

在线全文

在线全文

在线全文

在线全文

在线全文

请选择保存的检索档案： 新增检索档案 确定 取消

请选择收藏分类： 新增自定义分类 确定 取消

通借通还

建议与咨询留下您的常用邮箱和电话号码，以便我们向您反馈解决方案和替代方法

请选择保存的检索档案：

请选择收藏分类：