National Natural Science Foundation of China (NSFC)
31870726
China
National Natural Science Foundation of China (NSFC)
31630047
China
National Natural Science Foundation of China (NSFC)
31771610
China
Citation
Journal: Front Mol Biosci / Year: 2021 Title: Architecture of Dispatched, a Transmembrane Protein Responsible for Hedgehog Release. Authors: Yitian Luo / Guoyue Wan / Xuan Zhou / Qiuwen Wang / Yunbin Zhang / Juan Bao / Yao Cong / Yun Zhao / Dianfan Li / Abstract: The evolutionarily conserved Hedgehog (Hh) signaling pathway is crucial for programmed cell differentiation and proliferation. Dispatched (Disp) is a 12-transmembrane protein that plays a critical ...The evolutionarily conserved Hedgehog (Hh) signaling pathway is crucial for programmed cell differentiation and proliferation. Dispatched (Disp) is a 12-transmembrane protein that plays a critical role in the Hedgehog (Hh) signaling pathway by releasing the dually lipidated ligand HhN from the membrane, a prerequisite step to the downstream signaling cascade. In this study, we focus on the Disp from water bear, a primitive animal known as the most indestructible on Earth. Using a zebrafish model, we show that the water bear homolog possesses the function of Disp. We have solved its structure to a 6.5-Å resolution using single-particle cryogenic electron microscopy. Consistent with the evolutional conservation of the pathway, the water bear Disp structure is overall similar to the previously reported structures of the fruit fly and human homologs. Although not revealing much detail at this resolution, the water bear Disp shows a different conformation compared to published structures, suggesting that they represent different functional snapshots.
Average exposure time: 7.6 sec. / Electron dose: 60.8 e/Å2 / Detector mode: SUPER-RESOLUTION / Film or detector model: GATAN K2 SUMMIT (4k x 4k) / Num. of grids imaged: 3 / Num. of real images: 5380
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