Sites Important for PLCβ2 Activation by the G Protein βγ Subunit Map to the Sides of the β Propeller Structure

摘要: Abstract The βγ subunits of the heterotrimeric GTP-binding proteins (G proteins) that couple heptahelical, plasma membrane-bound receptors to intracellular effector enzymes or ion channels directly regulate several types effectors, including phospholipase Cβ and adenylyl cyclase. β subunit is made up two structurally different regions: an N-terminal α helix followed by a toroidal structure 7 blades, each which twisted sheet composed four anti-parallel strands (Wall, M. A., Coleman, D. E., Lee, Iniguez-Lluhi, J. Posner, B. Gilman, A. G., Sprang, S. R. (1995)Cell 83, 1047–1058; Lambright, Sondek, J., Bohm, Skiba, N. P., Hamm, H. Sigler, P. (1996) Nature 379, 311–319). We have previously shown sites for activation PLCβ2, PLCβ3, cyclase II overlap on “top” surface propeller, where Gα also binds (Li, Y., Sternweis, M., Charnecki, S., Smith, T. F., Neer, E. Kozasa, (1998)J. Biol. Chem. 273, 16265–16272). present study was undertaken identify regions side torus might be important interactions. mutations in outer G protein β1 as well loops connect adjacent strands. Our results suggest PLCβ2 involves residues blades 2, 6, propeller. tested three most severely affected activity against forms (ACI ACII). Both inhibition ACI ACII were unaffected these mutations, suggesting if contact strands, are from those PLCβ2. propose distinct sets contacts along sides propeller will define specificity interaction with effectors.