E. Buck et R. Iyengar, Modular design of G beta as the basis for reversible specificity in effector stimulation, J BIOL CHEM, 276(38), 2001, pp. 36014-36019
The G protein G beta gamma subunit complex stimulates effectors by direct i
nteractions utilizing extensive G beta regions over the surface of its prop
eller structure that faces the G alpha subunit. Our previous experiments ha
ve shown the resolved functions of signal transfer and general binding for
G beta regions involved in stimulation of the effector phospholipase C-beta
2, PLC-beta2, within the region G beta-(86-135), which comprises three beta
strands arranged in a structurally contiguous fashion (Buck, E., Li, J., C
hen, Y., Weng, G., Sacarlata, S., and Iyengar, R. (1999) Science 283, 1332-
1335). This raises an important question as to why mutagenesis studies indi
cate that an extensive set of sites all over the G beta propeller structure
and outside the 86-135 region are involved in G beta regulation of PLC-bet
a2. Using peptides to define functions of these G beta regions, we find tha
t G beta signaling to PLC-beta2 relies on a collection of modular signal tr
ansfer and general binding units, each with lower apparent affinity relativ
e to G beta gamma -PLC interactions. G beta-(42-54) functions as a signal t
ransfer region, G beta-(228-249) and G beta-(321-340) function in general b
inding, and G beta-(64-84) and G beta-(300-313) seem to play a structural r
ole rather than a direct contact with the effector. A substitution within t
he G beta-(42-54) signal transfer region that increases the K-act of this p
eptide for PLC-beta2 is accompanied by an increase in the observed maximal
extent of signal transfer. We conclude that the lower K-act for individual
signal transfer regions may result in a decrease in the maximal effect of s
ignal transfer. The spatial resolution of the signal transfer and general b
inding regions over a wide surface of GP allow geometrical constraints to a
chieve specificity even with relatively low affinity interactions.