The C-terminal GGAP motif of Hsp70 mediates substrate recognition and stress response in yeast

doi:10.1074/jbc.RA118.002691

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	The C-terminal GGAP motif of Hsp70 mediates substrate recognition and stress response in yeast
	Gong, Weibin 1; Hu, Wanhui1,2,4 ; Xu, Linan 3; Wu, Huiwen 1,2,5; Wu, Si 1,2; Zhang, Hong 1,2; Wang, Jinfeng 1; Jones, Gary W.3; Perrett, Sarah 1,2
	2018-11-16
发表期刊	JOURNAL OF BIOLOGICAL CHEMISTRY (IF:4.0[JCR-2023],4.4[5-Year])
ISSN	0021-9258
卷号	293 期号:46 页码:17663-17675
发表状态	已发表
DOI	10.1074/jbc.RA118.002691
摘要	The allosteric coupling of the highly conserved nucleotide- and substrate-binding domains of Hsp70 has been studied intensively. In contrast, the role of the disordered, highly variable C-terminal region of Hsp70 remains unclear. In many eukaryotic Hsp70s, the extreme C-terminal EEVD motif binds to the tetratricopeptide-repeat domains of Hsp70 co-chaperones. Here, we discovered that the TVEEVD sequence of Saccharomyces cerevisiae cytoplasmic Hsp70 (Ssa1) functions as a SUMO-interacting motif. A second C-terminal motif of approximate to 15 amino acids between the -helical lid and the extreme C terminus, previously identified in bacterial and eukaryotic organellar Hsp70s, is known to enhance chaperone function by transiently interacting with folding clients. Using structural analysis, interaction studies, fibril formation assays, and in vivo functional assays, we investigated the individual contributions of the -helical bundle and the C-terminal disordered region of Ssa1 in the inhibition of fibril formation of the prion protein Ure2. Our results revealed that although the -helical bundle of the Ssa1 substrate-binding domain (SBD) does not directly bind to Ure2, the SBD enhances the ability of Hsp70 to inhibit fibril formation. We found that a 20-residue C-terminal motif in Ssa1, containing GGAP and GGAP-like tetrapeptide repeats, can directly bind to Ure2, the Hsp40 co-chaperone Ydj1, and -synuclein, but not to the SUMO-like protein SMT3 or BSA. Deletion or substitution of the Ssa1 GGAP motif impaired yeast cell tolerance to temperature and cell-wall damage stress. This study highlights that the C-terminal GGAP motif of Hsp70 is important for substrate recognition and mediation of the heat shock response.
关键词	amyloid chaperone heat shock protein (HSP) nuclear magnetic resonance (NMR) protein structure Saccharomyces cerevisiae stress response SUMO-interacting motif (SIM) prion proline-rich motif
收录类别	EI ; SCIE ; SCI
语种	英语
资助项目	Science Foundation Ireland[SFI/13/ISCA/2845]
WOS研究方向	Biochemistry & Molecular Biology
WOS类目	Biochemistry & Molecular Biology
WOS记录号	WOS:000450409500001
出版者	AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
EI入藏号	20184706108711
EI主题词	Proteins
EI分类号	Organic Compounds:804.1 ; Food Products:822.3
WOS关键词	MOLECULAR CHAPERONE DNAK ; HEAT-SHOCK RESPONSE ; PRION PROTEIN URE2 ; SACCHAROMYCES-CEREVISIAE ; IN-VITRO ; ALPHA-SYNUCLEIN ; BINDING DOMAIN ; NOE ASSIGNMENT ; NMR ; HEAT-SHOCK-PROTEIN-70
原始文献类型	Article
引用统计	正在获取...
文献类型	期刊论文
条目标识符	https://kms.shanghaitech.edu.cn/handle/2MSLDSTB/28740
专题	iHuman研究所_特聘教授组_Kurt Wuthrich组
通讯作者	Jones, Gary W.; Perrett, Sarah
作者单位	1.Chinese Acad Sci, Inst Biophys, Ctr Excellence Biomacromol, Natl Lab Biomacromol, Beijing 100101, Peoples R China 2.Univ Chinese Acad Sci, Beijing 100049, Peoples R China 3.Maynooth Univ, Dept Biol, Maynooth W23 W6R7, Kildare, Ireland 4.ShanghaiTech Univ, iHuman Inst, Ren Bldg,393 Middle Huaxia Rd, Shanghai 201210, Peoples R China 5.Scripps Res Inst, Dept Integrat Struct & Computat Biol, La Jolla, CA 92037 USA
推荐引用方式 GB/T 7714	Gong, Weibin,Hu, Wanhui,Xu, Linan,et al. The C-terminal GGAP motif of Hsp70 mediates substrate recognition and stress response in yeast[J]. JOURNAL OF BIOLOGICAL CHEMISTRY,2018,293(46):17663-17675.
APA	Gong, Weibin.,Hu, Wanhui.,Xu, Linan.,Wu, Huiwen.,Wu, Si.,...&Perrett, Sarah.(2018).The C-terminal GGAP motif of Hsp70 mediates substrate recognition and stress response in yeast.JOURNAL OF BIOLOGICAL CHEMISTRY,293(46),17663-17675.
MLA	Gong, Weibin,et al."The C-terminal GGAP motif of Hsp70 mediates substrate recognition and stress response in yeast".JOURNAL OF BIOLOGICAL CHEMISTRY 293.46(2018):17663-17675.