作者
Gerti Beliu, Steffen Altrichter, Ramon Guixà-González, Mareike Hemberger, Ina Brauer, Anne-Kristin Dahse, Nicole Scholz, Robert Wieduwild, Alexander Kuhlemann, Hossein Batebi, Florian Seufert, Guillermo Pérez-Hernández, Peter W Hildebrand, Markus Sauer, Tobias Langenhan
发表日期
2021/3/4
期刊
Molecular Cell
卷号
81
期号
5
页码范围
905-921. e5
出版商
Cell Press
简介
Adhesion G protein-coupled receptors (aGPCRs)/family B2 GPCRs execute critical tasks during development and the operation of organs, and their genetic lesions are associated with human disorders, including cancers. Exceptional structural aGPCR features are the presence of a tethered agonist (TA) concealed within a GPCR autoproteolysis-inducing (GAIN) domain and their non-covalent heteromeric two-subunit layout. How the TA is poised for activation while maintaining this delicate receptor architecture is central to conflicting signaling paradigms that either involve or exclude aGPCR heterodimer separation. We investigated this matter in five mammalian aGPCR homologs (ADGRB3, ADGRE2, ADGRE5, ADGRG1, and ADGRL1) and demonstrate that intact aGPCR heterodimers exist at the cell surface, that the core TA region becomes unmasked in the cleaved GAIN domain, and that intra-GAIN domain …
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G Beliu, S Altrichter, R Guixà-González, M Hemberger… - Molecular cell, 2021