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-Structure paper
タイトル | Molecular basis of Wnt biogenesis, secretion, and Wnt7-specific signaling. |
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ジャーナル・号・ページ | Cell, Vol. 186, Issue 23, Page 5028-5040.e14, Year 2023 |
掲載日 | 2023年11月9日 |
![]() | Xiaofeng Qi / Qinli Hu / Nadia Elghobashi-Meinhardt / Tao Long / Hongwen Chen / Xiaochun Li / ![]() ![]() |
PubMed 要旨 | 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 ...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 engages the N-terminal domain of Wnt7a to activate Wnt7-specific signaling. |
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手法 | EM (単粒子) |
解像度 | 3.1 - 3.84 Å |
構造データ | EMDB-41764, PDB-8tzo: EMDB-41765, PDB-8tzp: EMDB-41768, PDB-8tzs: |
化合物 | ![]() ChemComp-PAM: ![]() ChemComp-POV: ![]() ChemComp-CA: |
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![]() | SIGNALING PROTEIN / MEMBRANE PROTEIN |