| Structural highlights
7kc4 is a 2 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
| | Method: | Electron Microscopy, Resolution 3.19Å |
| Ligands: | , , , , , |
| Resources: | FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT |
Disease
WLS_HUMAN The disease is caused by variants affecting the gene represented in this entry.
Function
WLS_HUMAN Regulates Wnt proteins sorting and secretion in a feedback regulatory mechanism. This reciprocal interaction plays a key role in the regulation of expression, subcellular location, binding and organelle-specific association of Wnt proteins (PubMed:34587386). Plays also an important role in establishment of the anterior-posterior body axis formation during development (By similarity).[1] [2] [3]
Publication Abstract from PubMed
Wnts are evolutionarily conserved ligands that signal at short range to regulate morphogenesis, cell fate, and stem cell renewal. The first and essential steps in Wnt secretion are their O-palmitoleation and subsequent loading onto the dedicated transporter Wntless/evenness interrupted (WLS/Evi). We report the 3.2 A resolution cryogenic electron microscopy (cryo-EM) structure of palmitoleated human WNT8A in complex with WLS. This is accompanied by biochemical experiments to probe the physiological implications of the observed association. The WLS membrane domain has close structural homology to G protein-coupled receptors (GPCRs). A Wnt hairpin inserts into a conserved hydrophobic cavity in the GPCR-like domain, and the palmitoleate protrudes between two helices into the bilayer. A conformational switch of highly conserved residues on a separate Wnt hairpin might contribute to its transfer to receiving cells. This work provides molecular-level insights into a central mechanism in animal body plan development and stem cell biology.
Structural Basis of WLS/Evi-Mediated Wnt Transport and Secretion.,Nygaard R, Yu J, Kim J, Ross DR, Parisi G, Clarke OB, Virshup DM, Mancia F Cell. 2021 Jan 7;184(1):194-206.e14. doi: 10.1016/j.cell.2020.11.038. Epub 2020 , Dec 23. PMID:33357447[4]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Bänziger C, Soldini D, Schütt C, Zipperlen P, Hausmann G, Basler K. Wntless, a conserved membrane protein dedicated to the secretion of Wnt proteins from signaling cells. Cell. 2006 May 5;125(3):509-22. PMID:16678095 doi:10.1016/j.cell.2006.02.049
- ↑ Bartscherer K, Pelte N, Ingelfinger D, Boutros M. Secretion of Wnt ligands requires Evi, a conserved transmembrane protein. Cell. 2006 May 5;125(3):523-33. PMID:16678096 doi:10.1016/j.cell.2006.04.009
- ↑ Chai G, Szenker-Ravi E, Chung C, Li Z, Wang L, Khatoo M, Marshall T, Jiang N, Yang X, McEvoy-Venneri J, Stanley V, Anzenberg P, Lang N, Wazny V, Yu J, Virshup DM, Nygaard R, Mancia F, Merdzanic R, Toralles MBP, Pitanga PML, Puri RD, Hernan R, Chung WK, Bertoli-Avella AM, Al-Sannaa N, Zaki MS, Willert K, Reversade B, Gleeson JG. A Human Pleiotropic Multiorgan Condition Caused by Deficient Wnt Secretion. N Engl J Med. 2021 Sep 30;385(14):1292-1301. PMID:34587386 doi:10.1056/NEJMoa2033911
- ↑ Nygaard R, Yu J, Kim J, Ross DR, Parisi G, Clarke OB, Virshup DM, Mancia F. Structural Basis of WLS/Evi-Mediated Wnt Transport and Secretion. Cell. 2021 Jan 7;184(1):194-206.e14. PMID:33357447 doi:10.1016/j.cell.2020.11.038
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