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-Structure paper
| タイトル | Structural insights into the activation of the chicken ROS1 receptor by the NEL/NICOL ligand complex. |
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| ジャーナル・号・ページ | Nat Commun, Vol. 17, Issue 1, Year 2026 |
| 掲載日 | 2026年2月24日 |
著者 | Weidong An / Xuewu Zhang / Xiao-Chen Bai / ![]() |
| PubMed 要旨 | The receptor tyrosine kinase ROS1 plays essential roles in cell growth and sperm maturation, yet its activation mechanism has remained poorly understood. Here, we report high-resolution cryo-electron ...The receptor tyrosine kinase ROS1 plays essential roles in cell growth and sperm maturation, yet its activation mechanism has remained poorly understood. Here, we report high-resolution cryo-electron microscopy (cryo-EM) structures of chicken ROS1 in its ligand-free form, in complex with its ligand NEL, and with the ligand/co-ligand complex NEL/NICOL. Unliganded ROS1 adopts an arc-shaped conformation. The interaction between NEL and ROS1 is mediated by the VWC2 domain of NEL and the β1 domain of ROS1. Binding of NICOL to the coiled-coil domain of NEL stabilizes NEL into a batwing-shaped asymmetric dimer, which can recruit only one ROS1 molecule due to steric hindrance. Structural analyses and biochemical results suggest that the 2:1 NEL/NICOL complexes further oligomerize through LamG-VWC4 domain interactions, facilitating the clustering of multiple ROS1 for its activation. Functional assays confirm that both NICOL and the multimerization of NEL/NICOL complexes are required for robust ROS1 signaling. Our findings establish NICOL as a critical co-ligand for ROS1 and suggest a distinct ligand-driven oligomerization mechanism for ROS1 activation. |
リンク | Nat Commun / PubMed:41735298 / PubMed Central |
| 手法 | EM (単粒子) |
| 解像度 | 2.7 - 4.2 Å |
| 構造データ | EMDB-71042, PDB-9oyz: EMDB-71047, PDB-9oz1: EMDB-71049, PDB-9oz6: EMDB-71051, PDB-9oz8: EMDB-71057, PDB-9ozc: EMDB-71058, PDB-9ozh: EMDB-71059, PDB-9ozi: |
| 化合物 | ![]() ChemComp-NAG: |
| 由来 |
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キーワード | STRUCTURAL PROTEIN / ROS1 / SIGNALING PROTEIN / NEL |
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