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Gα s protein C ‐terminal α‐helix at the interface: does the plasma membrane play a critical role in the Gα s protein functionality?
Author(s) -
Albrizio Stefania,
Caliendo Gabriella,
D'errico Gerardino,
Novellino Ettore,
Rovero Paolo,
D'ursi Anna Maria
Publication year - 2005
Publication title -
journal of peptide science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.475
H-Index - 66
eISSN - 1099-1387
pISSN - 1075-2617
DOI - 10.1002/psc.677
Subject(s) - heterotrimeric g protein , protein subunit , g protein , biophysics , chemistry , receptor , helix (gastropod) , g alpha subunit , conformational change , biochemistry , microbiology and biotechnology , biology , ecology , snail , gene
The heterotrimeric guanine nucleotide‐binding regulatory proteins (G proteins, Gαβγ) mediate the signalling process of a large number of receptors, known as G protein‐coupled receptors. The C ‐terminal domain of the heterotrimeric G protein α‐subunit plays a key role in the selective activation of G proteins by their cognate receptors. The interaction of this domain can take place at the end of a cascade including several successive conformational modifications. Gα s (350–394) is the 45‐mer peptide corresponding to the C ‐terminal region of the Gα s subunit. In the crystal structure of the Gα s subunit it encompasses the α4/β6 loop, the β6 β‐sheet segment and the α5 helix region. Following a previous study based on the synthesis, biological activity and conformational analysis of shorter peptides belonging to the same Gα s region, Gα s (350–394) was synthesized and investigated. The present study outlines the central role played by the residues involved in the α4/β6 loop and β6/α5 loops in the stabilization of the C ‐terminal Gα s α‐helix. H 2 O/ 2 H 2 O exchange experiments, and NMR diffusion experiments show interesting evidence concerning the interaction between the SDS micelles and the polypeptide. These data prompt intriguing speculations on the role of the intracellular environment/cellular membrane interface in the stabilization and functionality of the C ‐terminal Gα s region. Copyright © 2005 European Peptide Society and John Wiley & Sons, Ltd.