NADPH Is an Allosteric Regulator of HSCARG | |
Dai, Xueyu ; Li, Yiyu ; Meng, Geng ; Yao, Shun ; Zhao, Yanmei ; Yu, Quan ; Zhang, Jinfang ; Luo, Ming ; Zheng, Xiaofeng | |
刊名 | 分子生物学杂志
![]() |
2009 | |
关键词 | NADPH HSCARG mutant crystal structure allosteric regulator CELLULAR FUNCTIONS OXIDATIVE STRESS SENSOR PROTEIN BINDING TRANSCRIPTION INFLAMMATION ASSOCIATION NAD(+) DEATH NMRA |
DOI | 10.1016/j.jmb.2009.02.049 |
英文摘要 | NADP(H) is an important cofactor that controls many fundamental cellular processes. We have determined the crystal structure of HSCARG, a novel NADPH sensor, and found that it forms an asymmetrical dimer with only one subunit occupied by an NADPH molecule, and the two subunits have dramatically different conformations. To study the role of NADPH in affecting the structure and function of HSCARG, here, we constructed a series of HSCARG mutants to abolish NADPH binding ability. Protein structures of two mutants, R37A and Y81A, were solved by X-ray crystallography. The dimerization of wild-type and mutant HSCARG was studied by dynamic light scattering. Differences between the function of wild-type and mutant HSCARG were also compared. Our results show that binding of NADPH is necessary for HSCARG to form a stable asymmetric dimer. The conformation of the monomeric mutants was similar to that of NADPH-bound Molecule I in wild-type HSCARG, although some conformational changes were found in the NADPH binding site. Furthermore, we also noticed that abolition of NADPH binding ability changes the distribution of HSCARG in the cell and that these mutants without NADPH are more strongly associated with argininosuccinate synthetase as compared with wild-type HSCARG. These data suggest that NADPH functions as an allosteric regulator of the structure and function of HSCARG. In response to the changes in the NADPH/NADP(+) ratio within cells, HSCARG, as a redox sensor, associates and dissociates with NADPH to form a new dynamic equilibrium. This equilibrium, in turn, will tip the dimerization balance of the protein molecule and consequently controls the regulatory function of HSCARG. (C) 2009 Elsevier Ltd. All rights reserved.; Biochemistry & Molecular Biology; SCI(E); PubMed; 4; ARTICLE; 5; 1277-1285; 387 |
语种 | 英语 |
内容类型 | 期刊论文 |
源URL | [http://ir.pku.edu.cn/handle/20.500.11897/197668] ![]() |
专题 | 生命科学学院 |
推荐引用方式 GB/T 7714 | Dai, Xueyu,Li, Yiyu,Meng, Geng,et al. NADPH Is an Allosteric Regulator of HSCARG[J]. 分子生物学杂志,2009. |
APA | Dai, Xueyu.,Li, Yiyu.,Meng, Geng.,Yao, Shun.,Zhao, Yanmei.,...&Zheng, Xiaofeng.(2009).NADPH Is an Allosteric Regulator of HSCARG.分子生物学杂志. |
MLA | Dai, Xueyu,et al."NADPH Is an Allosteric Regulator of HSCARG".分子生物学杂志 (2009). |
个性服务 |
查看访问统计 |
相关权益政策 |
暂无数据 |
收藏/分享 |
除非特别说明,本系统中所有内容都受版权保护,并保留所有权利。
修改评论