Cryo-EM structure of human Wntless in complex with Wnt3a

doi:10.1038/s41467-021-24731-3

	Cryo-EM structure of human Wntless in complex with Wnt3a
	Zhong, Qing 1,2,3,4; Zhao, Yanyu 2,3,4; Ye, Fangfei 2,3,4; Xiao, Zaiyu 1,2,3,4; Huang, Gaoxingyu 2; Xu, Meng 2; Zhang, Yuanyuan 2; Zhan, Xiechao 2; Sun, Ke 2; Wang, Zhizhi5 ; Cheng, Shanshan5 ; Feng, Shan 2,6; Zhao, Xiuxiu 2,6; Zhang, Jizhong 2; Lu, Peilong 2,3,4; Xu, Wenqing5 ; Zhou, Qiang 2,3,4; Ma, Dan 2,3,4
	2021-07-27
发表期刊	NATURE COMMUNICATIONS (IF:14.7[JCR-2023],16.1[5-Year])
ISSN	2041-1723
卷号	12 期号:1
DOI	10.1038/s41467-021-24731-3
摘要	Wntless (WLS), an evolutionarily conserved multi-pass transmembrane protein, is essential for secretion of Wnt proteins. Wnt-triggered signaling pathways control many crucial life events, whereas aberrant Wnt signaling is tightly associated with many human diseases including cancers. Here, we report the cryo-EM structure of human WLS in complex with Wnt3a, the most widely studied Wnt, at 2.2 angstrom resolution. The transmembrane domain of WLS bears a GPCR fold, with a conserved core cavity and a lateral opening. Wnt3a interacts with WLS at multiple interfaces, with the lipid moiety on Wnt3a traversing a hydrophobic tunnel of WLS transmembrane domain and inserting into membrane. A beta -hairpin of Wnt3a containing the conserved palmitoleoylation site interacts with WLS extensively, which is crucial for WLS-mediated Wnt secretion. The flexibility of the Wnt3a loop/hairpin regions involved in the multiple binding sites indicates induced fit might happen when Wnts are bound to different binding partners. Our findings provide important insights into the molecular mechanism of Wnt palmitoleoylation, secretion and signaling. The transmembrane protein Wntless (WLS) is essential for the secretion of Wnt proteins, which are signaling molecules of the Wnt signaling pathways. Here, the authors present the 2.2 angstrom cryo-EM structure of human WLS in complex with Wnt3a and discuss mechanistic implications for the palmitoleoylation of Wnt3a that is required for WLS mediated Wnt secretion.
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收录类别	SCIE
语种	英语
WOS研究方向	Science & Technology - Other Topics
WOS类目	Multidisciplinary Sciences
WOS记录号	WOS:000683367300004
出版者	NATURE PORTFOLIO
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/128053
专题	生命科学与技术学院_PI研究组_许文青组生命科学与技术学院_博士生
通讯作者	Zhou, Qiang; Ma, Dan
作者单位	1.Fudan Univ, Shanghai, Peoples R China; 2.Westlake Univ, Sch Life Sci, Key Lab Struct Biol Zhejiang Prov, Hangzhou, Zhejiang, Peoples R China; 3.Westlake Lab Life Sci & Biomed, Hangzhou, Zhejiang, Peoples R China; 4.Westlake Inst Adv Study, Inst Biol, Hangzhou, Zhejiang, Peoples R China; 5.ShanghaiTech Univ, Sch Life Sci & Technol, Shanghai, Peoples R China; 6.Westlake Univ, Ctr Res Equipment & Facil, Biomed Res Core Facil, Mass Spectrometry Core Facil, Hangzhou, Zhejiang, Peoples R China
推荐引用方式 GB/T 7714	Zhong, Qing,Zhao, Yanyu,Ye, Fangfei,et al. Cryo-EM structure of human Wntless in complex with Wnt3a[J]. NATURE COMMUNICATIONS,2021,12(1).
APA	Zhong, Qing.,Zhao, Yanyu.,Ye, Fangfei.,Xiao, Zaiyu.,Huang, Gaoxingyu.,...&Ma, Dan.(2021).Cryo-EM structure of human Wntless in complex with Wnt3a.NATURE COMMUNICATIONS,12(1).
MLA	Zhong, Qing,et al."Cryo-EM structure of human Wntless in complex with Wnt3a".NATURE COMMUNICATIONS 12.1(2021).