Cryo-EM structure of human Wntless in complex with Wnt3a

Qing Zhong, Yanyu Zhao, Fangfei Ye, Zaiyu Xiao, Gaoxingyu Huang, Meng Xu, Yuanyuan Zhang, Xiechao Zhan, Ke Sun, Zhizhi Wang, Shanshan Cheng, Shan Feng, Xiuxiu Zhao, Jizhong Zhang, Peilong Lu, Wenqing Xu, Qiang Zhou () and Dan Ma ()
Additional contact information
Qing Zhong: Fudan University
Yanyu Zhao: Westlake University
Fangfei Ye: Westlake University
Zaiyu Xiao: Fudan University
Gaoxingyu Huang: Westlake University
Meng Xu: Westlake University
Yuanyuan Zhang: Westlake University
Xiechao Zhan: Westlake University
Ke Sun: Westlake University
Zhizhi Wang: ShanghaiTech University
Shanshan Cheng: ShanghaiTech University
Shan Feng: Westlake University
Xiuxiu Zhao: Westlake University
Jizhong Zhang: Westlake University
Peilong Lu: Westlake University
Wenqing Xu: ShanghaiTech University
Qiang Zhou: Westlake University
Dan Ma: Westlake University

Nature Communications, 2021, vol. 12, issue 1, 1-8

Abstract: Abstract 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 Å 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 β-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.

Date: 2021
References: Add references at CitEc
Citations:

Downloads: (external link)
https://www.nature.com/articles/s41467-021-24731-3 Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:12:y:2021:i:1:d:10.1038_s41467-021-24731-3

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/s41467-021-24731-3

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().