National Natural Science Foundation of China (NSFC)
31570748
中国
National Natural Science Foundation of China (NSFC)
U1632127
中国
Chinese Academy of Sciences
XDB37020204
中国
Chinese Academy of Sciences
QYZDB-SSW-SMC037
中国
引用
ジャーナル: Structure / 年: 2021 タイトル: Cryo-EM study of patched in lipid nanodisc suggests a structural basis for its clustering in caveolae. 著者: Yitian Luo / Guoyue Wan / Xiang Zhang / Xuan Zhou / Qiuwen Wang / Jialin Fan / Hongmin Cai / Liya Ma / Hailong Wu / Qianhui Qu / Yao Cong / Yun Zhao / Dianfan Li / 要旨: The 12-transmembrane protein Patched (Ptc1) acts as a suppressor for Hedgehog (Hh) signaling by depleting sterols in the cytoplasmic membrane leaflet that are required for the activation of ...The 12-transmembrane protein Patched (Ptc1) acts as a suppressor for Hedgehog (Hh) signaling by depleting sterols in the cytoplasmic membrane leaflet that are required for the activation of downstream regulators. The positive modulator Hh inhibits Ptc1's transporter function by binding to Ptc1 and its co-receptors, which are locally concentrated in invaginated microdomains known as caveolae. Here, we reconstitute the mouse Ptc1 into lipid nanodiscs and determine its structure using single-particle cryoelectron microscopy. The structure is overall similar to those in amphipol and detergents but displays various conformational differences in the transmembrane region. Although most particles show monomers, we observe Ptc1 dimers with distinct interaction patterns and different membrane curvatures, some of which are reminiscent of caveolae. We find that an extramembranous "hand-shake" region rich in hydrophobic and aromatic residues mediates inter-Ptc1 interactions under different membrane curvatures. Our data provide a plausible framework for Ptc1 clustering in the highly curved caveolae.