7drt
From Proteopedia
Human Wntless in complex with Wnt3a
Structural highlights
DiseaseWNT3A_HUMAN Idiopathic juvenile osteoporosis. FunctionWNT3A_HUMAN Ligand for members of the frizzled family of seven transmembrane receptors (Probable). Functions in the canonical Wnt signaling pathway that results in activation of transcription factors of the TCF/LEF family (PubMed:20093360, PubMed:21244856, PubMed:24841207, PubMed:26902720). Required for normal embryonic mesoderm development and formation of caudal somites. Required for normal morphogenesis of the developing neural tube (By similarity). Mediates self-renewal of the stem cells at the bottom on intestinal crypts (in vitro) (PubMed:26902720).[UniProtKB:P27467][1] [2] [3] [4] Publication Abstract from PubMedWntless (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 A 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. Cryo-EM structure of human Wntless in complex with Wnt3a.,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 Nat Commun. 2021 Jul 27;12(1):4541. doi: 10.1038/s41467-021-24731-3. PMID:34315898[5] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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Categories: Homo sapiens | Large Structures | Huang G | Lu P | Ma D | Xiao Z | Xu W | Ye F | Zhang Y | Zhao Y | Zhong Q | Zhou Q
