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Structural basis for the recognition of K48-linked Ub chain by proteasomal receptor Rpn13

文献类型：期刊论文

作者Tang, Chun1,4,6; Zhang, Wei-Ping2,3; Liu, Kan6; Wang, Yi2,3; Gong, Zhou6; Yang, Ju4,6; Yi, Hua-Wei4,6; Dong, Xu6; Liu, Zhu5,6
刊名CELL DISCOVERY
出版日期2019-04-02
卷号5页码:15
ISSN号2056-5968
DOI10.1038/s41421-019-0089-7
英文摘要The interaction between K48-linked ubiquitin (Ub) chain and Rpn13 is important for proteasomal degradation of ubiquitinated substrate proteins. Only the complex structure between the N-terminal domain of Rpn13 (Rpn13(NTD)) and Ub monomer has been characterized, while it remains unclear how Rpn13 specifically recognizes K48-linked Ub chain. Using single-molecule FRET, here we show that K48-linked diubiquitin (K48-diUb) fluctuates among distinct conformational states, and a preexisting compact state is selectively enriched by Rpn13(NTD). The same binding mode is observed for full-length Rpn13 and longer K48-linked Ub chain. Using solution NMR spectroscopy, we have determined the complex structure between Rpn13(NTD) and K48-diUb. In this structure, Rpn13(NTD )simultaneously interacts with proximal and distal Ub subunits of K48-diUb that remain associated in the complex, thus corroborating smFRET findings. The proximal Ub interacts with Rpn13(NTD) similarly as the Ub monomer in the known Rpn13(NTD):Ub structure, while the distal Ub binds to a largely electrostatic surface of Rpn13(NTD). Thus, a charge-reversal mutation in Rpn13 NTD weakens the interaction between Rpn13 and K48-linked Ub chain, causing accumulation of ubiquitinated proteins. Moreover, physical blockage of the access of the distal Ub to Rpn13(NTD) with a proximity-attached Ub monomer can disrupt the interaction between Rpn13 and K48-diUb. Taken together, the bivalent interaction of K48-linked Ub chain with Rpn13 provides the structural basis for Rpn13 linkage selectivity, which opens a new window for modulating proteasomal function.
WOS关键词PROTEIN-PROTEIN COMPLEXES ; UBIQUITIN ; DIUBIQUITIN ; SUBUNIT ; DOCKING ; MODEL ; FRET ; DYNAMICS ; ACCURATE ; NUCLEAR
资助项目National Key R&D Program of China[2018YFA0507700] ; National Key R&D Program of China[2016YFA0501200] ; National Key R&D Program of China[2017YFA0505400] ; National Natural Science Foundation of China[91753132] ; National Natural Science Foundation of China[31770799] ; National Natural Science Foundation of China[81573400] ; National Natural Science Foundation of China[31500595] ; National Natural Science Foundation of China[31400735] ; National Natural Science Foundation of China[31400644]
WOS研究方向Cell Biology
语种英语
WOS记录号WOS:000466761300001
出版者NATURE PUBLISHING GROUP
资助机构National Key R&D Program of China ; National Key R&D Program of China ; National Natural Science Foundation of China ; National Natural Science Foundation of China ; National Key R&D Program of China ; National Key R&D Program of China ; National Natural Science Foundation of China ; National Natural Science Foundation of China ; National Key R&D Program of China ; National Key R&D Program of China ; National Natural Science Foundation of China ; National Natural Science Foundation of China ; National Key R&D Program of China ; National Key R&D Program of China ; National Natural Science Foundation of China ; National Natural Science Foundation of China
源URL[http://ir.wipm.ac.cn/handle/112942/13713]  
专题中国科学院武汉物理与数学研究所
通讯作者Tang, Chun; Zhang, Wei-Ping
作者单位1.Wuhan Natl Lab Optoelect, Wuhan 430074, Hubei, Peoples R China
2.Zhejiang Univ, Sch Med, Zhejiang Prov Key Lab Mental Disorders Management, Hangzhou 310027, Zhejiang, Peoples R China
3.Zhejiang Univ, Inst Neurosci, Dept Pharmacol, Minist Hlth China,Key Lab Med Neurobiol,Sch Med, Hangzhou 310027, Zhejiang, Peoples R China
4.Univ Chinese Acad Sci, Beijing 100049, Peoples R China
5.Huazhong Agr Univ, Coll Life Sci & Technol, Natl Key Lab Crop Genet Improvement, Wuhan 430070, Hubei, Peoples R China
6.Chinese Acad Sci, Natl Ctr Magnet Resonance Wuhan, State Key Lab Magnet Resonance & Atom Mol Phys, Wuhan Inst Phys & Math,CAS Key Lab Magnet Resonan, Wuhan 430071, Hubei, Peoples R China
推荐引用方式
GB/T 7714		 Tang, Chun,Zhang, Wei-Ping,Liu, Kan,et al. Structural basis for the recognition of K48-linked Ub chain by proteasomal receptor Rpn13[J]. CELL DISCOVERY,2019,5:15.
APA Tang, Chun.,Zhang, Wei-Ping.,Liu, Kan.,Wang, Yi.,Gong, Zhou.,...&Liu, Zhu.(2019).Structural basis for the recognition of K48-linked Ub chain by proteasomal receptor Rpn13.CELL DISCOVERY,5,15.
MLA Tang, Chun,et al."Structural basis for the recognition of K48-linked Ub chain by proteasomal receptor Rpn13".CELL DISCOVERY 5(2019):15.

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来源：武汉物理与数学研究所

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