8tzp
From Proteopedia
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== Disease == | == Disease == | ||
| - | [https://www.uniprot.org/uniprot/ | + | [https://www.uniprot.org/uniprot/WNT7A_HUMAN WNT7A_HUMAN] Phocomelia, Schinzel type;Fuhrmann syndrome. The disease is caused by mutations affecting the gene represented in this entry. The disease is caused by mutations affecting the gene represented in this entry. |
== Function == | == Function == | ||
| - | [https://www.uniprot.org/uniprot/ | + | [https://www.uniprot.org/uniprot/WNT7A_HUMAN WNT7A_HUMAN] Ligand for members of the frizzled family of seven transmembrane receptors. Probable developmental protein. Signaling by Wnt-7a allows sexually dimorphic development of the mullerian ducts (By similarity). |
| + | <div style="background-color:#fffaf0;"> | ||
| + | == Publication Abstract from PubMed == | ||
| + | Wnt proteins are enzymatically lipidated by Porcupine (PORCN) in the ER and bind to Wntless (WLS) for intracellular transport and secretion. Mechanisms governing the transfer of these low-solubility Wnts from the ER to the extracellular space remain unclear. Through structural and functional analyses of Wnt7a, a crucial Wnt involved in central nervous system angiogenesis and blood-brain barrier maintenance, we have elucidated the principles of Wnt biogenesis and Wnt7-specific signaling. The Wnt7a-WLS complex binds to calreticulin (CALR), revealing that CALR functions as a chaperone to facilitate Wnt transfer from PORCN to WLS during Wnt biogenesis. Our structures, functional analyses, and molecular dynamics simulations demonstrate that a phospholipid in the core of Wnt-bound WLS regulates the association and dissociation between Wnt and WLS, suggesting a lipid-mediated Wnt secretion mechanism. Finally, the structure of Wnt7a bound to RECK, a cell-surface Wnt7 co-receptor, reveals how RECK(CC4) engages the N-terminal domain of Wnt7a to activate Wnt7-specific signaling. | ||
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| + | Molecular basis of Wnt biogenesis, secretion, and Wnt7-specific signaling.,Qi X, Hu Q, Elghobashi-Meinhardt N, Long T, Chen H, Li X Cell. 2023 Nov 9;186(23):5028-5040.e14. doi: 10.1016/j.cell.2023.09.021. Epub , 2023 Oct 17. PMID:37852257<ref>PMID:37852257</ref> | ||
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| + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | ||
| + | </div> | ||
| + | <div class="pdbe-citations 8tzp" style="background-color:#fffaf0;"></div> | ||
== References == | == References == | ||
<references/> | <references/> | ||
Current revision
Structure of human Wnt7a bound to WLS and RECK
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Categories: Homo sapiens | Large Structures | Hu Q | Li X | Qi X
