7DRT

Human Wntless in complex with Wnt3a

Summary for 7DRT

• Entry DOI: 10.2210/pdb7drt/pdb
• EMDB information: 30827
• Descriptor: Protein Wnt-3a, Protein wntless homolog, 2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose, ... (8 entities in total)
• Functional Keywords: wnt signaling; wnt secretion; wls; wnt3a; cryo-em; palmitoleoylation; membrane protein, membrane protein
• Biological source: Homo sapiens (Human); More
• Total number of polymer chains: 2
• Total formula weight: 104890.22

Authors

Zhong, Q.,Zhao, Y.,Ye, F.,Xiao, Z.,Huang, G.,Zhang, Y.,Lu, P.,Xu, W.,Zhou, Q.,Ma, D. (deposition date: 2020-12-29, release date: 2021-07-14, Last modification date: 2024-10-30)

Primary citation

Zhong, Q.,Zhao, Y.,Ye, F.,Xiao, Z.,Huang, G.,Xu, M.,Zhang, Y.,Zhan, X.,Sun, K.,Wang, Z.,Cheng, S.,Feng, S.,Zhao, X.,Zhang, J.,Lu, P.,Xu, W.,Zhou, Q.,Ma, D.
Cryo-EM structure of human Wntless in complex with Wnt3a.
Nat Commun, 12:4541-4541, 2021

PubMed 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.

PubMed: 34315898
DOI: 10.1038/s41467-021-24731-3

Experimental method

ELECTRON MICROSCOPY (2.2 Å)