The C terminal domain of the heterotrimenc G protein alpha subunits plays a key role in selective activation of G proteins by their cognate receptors Several C terminal fragments of Galpha (from 11 to 21 residues) were recently synthesized The ability of these peptides to stimulate agonist binding was found to be related to their size Galphas(380-394) is a 15 mer peptide of intermediate length among, those synthesized and tested that displays a biological activity surprisingly weak compared with that of the corresponding 21 mer peptide shown to be the most active In the present investigation Galpha (380-394) was subjected to a conformational. NMR analysis in a fluorinated isotropic environment An NMR structure calculated on the basis of the data derived from conventional 1D and 2D homonuclear experiments shows that the C terminal residues of Ga (380-394) are involved in a helical arrangement whose length is comparable to that of the most active 21 mer peptide A comparative structural refinement of the NMR structures of Galpha (380-394) and Galpha (374-394)C(379)A was performed using molecular dynamics calculations The results give structural elements to interpret the role played by both the backbone conformation and the side chain arrangement in determining the activity of the G protein C terminal fragments The orientation of the side chains allows the peptides to assume contacts crucial for the G protein/receptor interaction In the 15 mer peptide the lack as well as the disorder of some N terminal residues could explain the low biological activity observed Copyright (C) 2002 European Peptide Society and John Wiley Sons Ltd.
|Autori interni:||MAZZONI, MARIA ROSA|
|Autori:||D'Ursi A; Albrizio S; Greco G; Mazzeo S; Mazzoni M; Novellino E; Rovero P|
|Titolo:||Conformational analysis of the Galphas protein C-terminal region|
|Anno del prodotto:||2002|
|Appare nelle tipologie:||1.1 Articolo in rivista|