A RhoA structure with switch II flipped outward revealed the conformational dynamics of switch II region
文献类型：期刊论文
| 作者 | Jiang, Hao6,7,8; Zu, Shijia6,7; Lu, Yu5; Sun, Zhongya4,7; Adeerjiang, Akejiang6,7; Guo, Qiao5; Zhang, Huimin3,7; Dong, Chen6,7; Wu, Qiqi7; Ding, Hong7
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| 刊名 | JOURNAL OF STRUCTURAL BIOLOGY
 |
| 出版日期 | 2023-06-01 |
| 卷号 | 215期号:2页码:107942 |
| 关键词 | Small GTPases Crystal structures of RhoA Dynamics of switch II Molecular dynamics simulations Allosteric pocket |
| DOI | 10.1016/j.jsb.2023.107942 |
| 文献子类 | Article |
| 英文摘要 | Small GTPase RhoA switches from GTP-bound state to GDP-bound state by hydrolyzing GTP, which is acceler-ated by GTPases activating proteins (GAPs). However, less study of RhoA structural dynamic changes was conducted during this process, which is essential for understanding the molecular mechanism of GAP dissocia-tion. Here, we solved a RhoA structure in GDP-bound state with switch II flipped outward. Because lacking the intermolecular interactions with guanine nucleotide, we proposed this conformation of RhoA could be an in-termediate after GAP dissociation. Further molecular dynamics simulations found the conformational changes of switch regions are indeed existing in RhoA and involved in the regulation of GAP dissociation and GEF recog-nition. Besides, the guanine nucleotide binding pocket extended to switch II region, indicating a potential druggable cavity for RhoA. Taken together, our study provides a deeper understanding of the dynamic properties of RhoA switch regions and highlights the direction for future drug development. |
| WOS关键词 | CRYSTAL-STRUCTURE ; SMALL GTPASES ; RAS ; GTP ; ACTIVATION ; EXCHANGE ; BINDING ; GAPS ; FORM ; GEFS |
| WOS研究方向 | Biochemistry & Molecular Biology ; Biophysics ; Cell Biology |
| 语种 | 英语 |
| 出版者 | ACADEMIC PRESS INC ELSEVIER SCIENCE |
| WOS记录号 | WOS:000965770900001 |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/309686]  |
| 专题 | 新药研究国家重点实验室 |
| 通讯作者 | Liang, Zhongjie; Luo, Cheng |
| 作者单位 | 1.Ensem Therapeut Inc, 200 Boston Ave, Medford, MA 02155 USA 2.Chinese Acad Sci, Zhongshan Inst Drug Discovery, Shanghai Inst Mat Med, Zhongshan 528437, Peoples R China; 3.Shanghai Tech Univ, Sch Life Sci & Technol, 100 Haike Rd, Shanghai 201210, Peoples R China; 4.Harbin Inst Technol, Sch Life Sci & Technol, Harbin 150001, Peoples R China; 5.Soochow Univ, Ctr Syst Biol, Sch Biol & Basic Med Sci, Dept Bioinformat, Suzhou 215123, Peoples R China; 6.Univ Chinese Acad Sci UCAS, 19 Yuquan Rd, Beijing 100049, Peoples R China; 7.Chinese Acad Sci, Shanghai Inst Mat Med, State Key Lab Drug Res, 555 Zuchongzhi Rd, Shanghai 201203, Peoples R China; 8.UCAS, Hangzhou Inst Adv Study, Sch Pharmaceut Sci & Technol, Hangzhou 310024, Peoples R China; |
| 推荐引用方式 GB/T 7714 | Jiang, Hao,Zu, Shijia,Lu, Yu,et al. A RhoA structure with switch II flipped outward revealed the conformational dynamics of switch II region[J]. JOURNAL OF STRUCTURAL BIOLOGY,2023,215(2):107942. |
| APA | Jiang, Hao.,Zu, Shijia.,Lu, Yu.,Sun, Zhongya.,Adeerjiang, Akejiang.,...&Luo, Cheng.(2023).A RhoA structure with switch II flipped outward revealed the conformational dynamics of switch II region.JOURNAL OF STRUCTURAL BIOLOGY,215(2),107942. |
| MLA | Jiang, Hao,et al."A RhoA structure with switch II flipped outward revealed the conformational dynamics of switch II region".JOURNAL OF STRUCTURAL BIOLOGY 215.2(2023):107942. |
入库方式： OAI收割
来源：上海药物研究所
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