8tzo

From Proteopedia

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Structure of human Wnt7a bound to WLS and CALR

Structural highlights

8tzo is a 3 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 3.1Å
Ligands:	, , , , , ,
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Disease

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

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).

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.

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^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Qi X, Hu Q, Elghobashi-Meinhardt N, Long T, Chen H, Li X. Molecular basis of Wnt biogenesis, secretion, and Wnt7-specific signaling. Cell. 2023 Nov 9;186(23):5028-5040.e14. PMID:37852257 doi:10.1016/j.cell.2023.09.021