Article,
Peptide G protein agonists from a phage display library
Biochem Pharmacol, 65 (6): 961-7 (March 2003)Hessling, Jutta Lohse, Martin J Klotz, Karl-Norbert Research Support, Non-U.S. Gov't England Biochemical pharmacology Biochem Pharmacol. 2003 Mar 15;65(6):961-7..
Abstract
G proteins may serve as targets for pharmacological activation of
signaling pathways bypassing the regulatory events that may counteract
the effect of the external stimulus on the level of receptors. We
sought to identify peptides as lead structures interacting with G
proteins utilizing a commercially available phage-display library.
The heptapeptide library was screened for binding to human G alpha(i1)
which was modified with a hexahistidine tag and immobilized on a
Ni(2+)-coated surface. After several rounds of phage selection a
number of phage clones with consensus sequences were found. Peptides
with such sequences were chemically synthesized and their effect
on 35SGTP gamma S binding to G alpha(i1) and other G protein alpha
subunits was determined. Through this process two peptide 'families'
with the capability to activate G proteins were identified. The peptides
showed no structural similarity to known peptide or nonpeptide G
protein activators with a cationic amphiphilic structure like mastoparan
or alkylamines. The functional relevance of the peptide-G protein
interaction was shown by an increased sensitivity for guanine nucleotides
of high-affinity agonist binding to A(1) adenosine receptors. The
peptide G protein activators may, therefore, serve as novel tools
for further investigation of receptor-independent activation of G
proteins.
Tags
- *peptide
- animals
- binding
- cell
- cho
- cricetinae
- gtp-binding
- heterotrimeric
- library
- peptides/metabolism
- proteins/metabolism
- signal
- sites
- transduction
