Plexin-B1 is a unique transmembrane receptor, because upon activation by extracellular ligand, several intracellular regions interact directly with several small GPTases of Rho and Rap familiesthat have roles in neural development and axon growth guidance. For functional expression,plexin-B1 acts as a GTPase-activating protein (converting GTP to GDP) for Rap-GTPases (Rap1b). The association with Rho-GTPases (Rnd1/Rac1) has a role in plexin-B1 functional regulation, but the mechanism is unclear. Here, we present a study of the interactions of plexin-B1 intracellular domain with Rho-GTPases (Rnd1/Rac1) at a model membrane through all-atom molecular dynamics simulations up to 15 μs. The level of activation of plexin-B1 was found to be related to the oligomeric forms of plexin-B1 (monomer, dimer and trimer). Small Rho-GTPases---Rnd1 and Rac1, regulate the activity of plexin-B1 through altering the organizations of plexin-B1 momomer, dimer and trimer. The steric positioning of specific functional regions relative to the membrane is vital for the GAP activity. The roles of plexin-B1 oligomerization and Rho-GTPases in regulating the function of Plexin-B1 were further confirmed experimentally by protein binding and protein activity assays.

Unveiling a regulation mechanism of small GPTases on activity of plexin-B1 membrane receptor

256th National Meeting (2018)

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