Structure of BAI1/ELMO2 complex reveals an action mechanism of adhesion GPCRs via ELMO family scaffolds.
basic_science · Level V
Where this comes from
- Record sourced from PubMed, PMID 30604775.
- Also identified by DOI 10.1038/s41467-018-07938-9 and PMC identifier 6318265.
- Licence recorded as CC BY.
- The licence permits redistribution, so the abstract is shown in full and the full text is available from the publisher.
Abstract
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 a recognition mode similar to that of BAI/ELMO interactions. Finally, we map disease-causing mutations of BAI and ELMO and analyze their effects on complex formation.
Medical subject headings
- Adaptor Proteins, Signal Transducing
- Angiogenic Proteins
- Cytoskeletal Proteins
- Protein Interaction Domains and Motifs
- Receptors, G-Protein-Coupled