Modular Design of Gβ as the Basis for Reversible Specificity in Effector Stimulation

Elizabeth Buck, Ravi Iyengar

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10 Scopus citations

Abstract

The G protein Gβγ subunit complex stimulates effectors by direct interactions utilizing extensive Gβ regions over the surface of its propeller structure that faces the Gα subunit. Our previous experiments have shown the resolved functions of signal transfer and general binding for Gβ regions involved in stimulation of the effector phospholipase C-β2, PLC-β2, within the region Gβ-(86-135), which comprises three β strands arranged in a structurally contiguous fashion (Buck, E., Li, J., Chen, Y., Weng, G., Sacarlata, S., and Iyengar, R. (1999) Science 283, 1332-1335). This raises an important question as to why mutagenesis studies indicate that an extensive set of sites all over the Gβ propeller structure and outside the 86-135 region are involved in Gβ regulation of PLC-β2. Using peptides to define functions of these Gβ regions, we find that Gβ signaling to PLC-β2 relies on a collection of modular signal transfer and general binding units, each with lower apparent affinity relative to Gβγ-PLC interactions. Gβ-(42-54) functions as a signal transfer region, Gβ-(228-249) and Gβ-(321-340) function in general binding, and Gβ-(64-84) and Gβ-(300-313) seem to play a structural role rather than a direct contact with the effector. A substitution within the Gβ-(42-54) signal transfer region that increases the Kact of this peptide for PLC-β2 is accompanied by an increase in the observed maximal extent of signal transfer. We conclude that the lower Kact for individual signal transfer regions may result in a decrease in the maximal effect of signal transfer. The spatial resolution of the signal transfer and general binding regions over a wide surface of Gβ allow geometrical constraints to achieve specificity even with relatively low affinity interactions.

Original languageEnglish
Pages (from-to)36014-36019
Number of pages6
JournalJournal of Biological Chemistry
Volume276
Issue number38
DOIs
StatePublished - 21 Sep 2001

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