biostudies-literatureUnknown10(1)Weng ZThe brain-specific angiogenesis inhibitor (BAI) subfamily of adhesion G protein-coupled receptors (aGPCRs) plays crucial roles in diverse cellular processes including phagocytosis, myoblast fusion, and synaptic development through the ELMO/DOCK/Rac signaling pathway, although the underlying molecular mechanism is not well understood. Here, we demonstrate that an evolutionarily conserved fragment located in the C-terminal cytoplasmic tail of BAI-aGPCRs is specifically recognized by the RBD-ARR-ELMO (RAE) supramodule of the ELMO family scaffolds. The crystal structures of ELMO2-RAE and its complex with BAI1 uncover the molecular basis of BAI/ELMO interactions. Based on the complex structure we identify aGPCR-GPR128 as another upstream receptor for the ELMO family scaffolds, most likely with Nature communications51https://www.ebi.ac.uk/biostudies/studies/S-EPMC6318265biostudies-literatureStructure of BAI1/ELMO2 complex reveals an action mechanism of adhesion GPCRs via ELMO family scaffolds.PMC6318265Wu ZZhu JWeng ZSitu CLin LZhang RfalseStructure of BAI1/ELMO2 complex reveals an action mechanism of adhesion GPCRs via ELMO family scaffolds.The brain-specific angiogenesis inhibitor (BAI) subfamily of adhesion G protein-coupled receptors (aGPCRs) plays crucial roles in diverse cellular processes including phagocytosis, myoblast fusion, and synaptic development through the ELMO/DOCK/Rac signaling pathway, although the underlying molecular mechanism is not well understood. Here, we demonstrate that an evolutionarily conserved fragment located in the C-terminal cytoplasmic tail of BAI-aGPCRs is specifically recognized by the RBD-ARR-ELMO (RAE) supramodule of the ELMO family scaffolds. The crystal structures of ELMO2-RAE and its complex with BAI1 uncover the molecular basis of BAI/ELMO interactions. Based on the complex structure we identify aGPCR-GPR128 as another upstream receptor for the ELMO family scaffolds, most likely with 2019-01-01T00:00:00Z2019 Jan2026-07-16T19:37:25.09Z2019-03-26T22:34:00ZS-EPMC63182653060477510.1038/s41467-018-07938-9