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-Structure paper
| タイトル | Structures and receptor binding activities of merbecovirus spike proteins reveal key signatures for human DPP4 adaptation. |
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| ジャーナル・号・ページ | Sci Adv, Vol. 11, Issue 28, Page eadv7296, Year 2025 |
| 掲載日 | 2025年7月11日 |
著者 | Hang Yuan / Jingjing Wang / Yong Ma / Zimu Li / Xijie Gao / Gul Habib / Banghui Liu / Jing Chen / Jun He / Peng Zhou / Zheng-Li Shi / Xinwen Chen / Xiaoli Xiong / ![]() |
| PubMed 要旨 | Merbecoviruses from bats, pangolins, and hedgehogs pose significant zoonotic threats, with a limited understanding of receptor binding by their spike (S) proteins. Here, we report cryo-EM structures ...Merbecoviruses from bats, pangolins, and hedgehogs pose significant zoonotic threats, with a limited understanding of receptor binding by their spike (S) proteins. Here, we report cryo-EM structures of GD-BatCoV (BtCoV-422) and SE-PangolinCoV (MjHKU4r-CoV-1) RBDs in complex with human DPP4 (hDPP4). These structures exhibit a substantial offset in their hDPP4 interaction interfaces, revealing a conserved hydrophobic cluster as a convergent signature of DPP4 binding within the MERS-HKU4 clade of merbecoviruses. Structure-guided mutagenesis demonstrates that favorable interactions are distributed across multiple receptor binding motif (RBM) regions, working synergistically to confer high-affinity hDPP4 binding. Swapping of the merbecovirus RBM regions indicate limited plasticity and interchangeability among these regions. In addition, we report cryo-EM structures of six merbecovirus S-trimers. Structure-based phylogenetics suggests that hDPP4-binding merbecoviruses undergo convergent evolution, while ACE2-binding merbecoviruses exhibit diversification in their binding mechanisms. These findings offer critical insights into merbecovirus receptor utilization, providing a structural understanding for future surveillance. |
リンク | Sci Adv / PubMed:40644548 / PubMed Central |
| 手法 | EM (単粒子) |
| 解像度 | 2.8 - 3.8 Å |
| 構造データ | EMDB-61600, PDB-9jmf: EMDB-61601, PDB-9jmg: EMDB-61602, PDB-9jmh: EMDB-61603, PDB-9jmi: EMDB-61604, PDB-9jmj: EMDB-61606, PDB-9jmm: EMDB-61607, PDB-9jmn: EMDB-61608, PDB-9jmo: EMDB-61609, PDB-9jmp: |
| 化合物 | ![]() ChemComp-NAG: ![]() ChemComp-EIC: ![]() ChemComp-FOL: |
| 由来 |
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キーワード | VIRAL PROTEIN / spike protein / complex |
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coronavirus neoromicia/pml-phe1/rsa/2011 (ウイルス)
homo sapiens (ヒト)
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