State-selective binding peptides for heterotrimeric G-protein subunits: Novel tools for investigating G-protein signaling dynamics

Christopher A. Johnston, Francis S. Willard, J. Kevin Ramer, Rainer Blaesius, C. Natalia Roques, David P. Siderovski

Research output: Contribution to journalReview articlepeer-review

8 Scopus citations

Abstract

Heterotrimeric G-proteins, comprising Gα, Gβ, and Gγ subunits, are molecular switches that regulate numerous signaling pathways involved in cellular physiology. This characteristic is achieved by the adoption of two principal states: an inactive state in which GDP-bound Gα is complexed with the Gβγ dimer, and an active state in which GTP-bound Gα is freed of its Gβγ binding partner. Structural studies have illustrated the basis for the distinct conformations of these states which are regulated by alterations in three precise 'switch regions' of the Gα subunit. Discrete differences in conformation between GDP- and GTP-bound Gα underlie its nucleotide-dependent protein-protein interactions (e.g., with Gβγ/receptor and effectors, respectively) that are critical for maintaining their proper nucleotide cycling and signaling properties. Recently, several screening approaches have been used to identify peptide sequences capable of interacting with Gα (and free Gβγ) in nucleotide-dependent fashions. These peptides have demonstrated applications in direct modulation of the nucleotide cycle, assessing the structural basis for aspects of Gα and Gβγ signaling, and serving as biosensor tools in assays for Gα activation including high throughput drug screening. In this review, we highlight some of the methods used for such discoveries and discuss the insights that can be gleaned from application of these identified peptides.

Original languageEnglish
Pages (from-to)370-381
Number of pages12
JournalCombinatorial Chemistry and High Throughput Screening
Volume11
Issue number5
DOIs
StatePublished - Jun 2008

Fingerprint Dive into the research topics of 'State-selective binding peptides for heterotrimeric G-protein subunits: Novel tools for investigating G-protein signaling dynamics'. Together they form a unique fingerprint.

Cite this