It has recently been reported that synthetic peptides corresponding to the C-terminal sequence of Gα, can be used to study the molecular mechanisms of interaction between this protein and G protein coupled receptors (Hamm et al., Science, 1988, Vol. 241, pp. 832-835). A conformational analysis on a 11 amino acids peptide from the Gα(s) C-terminus, Gα(s)(384-394) (H- QRMHLRQYELL-OH), was performed by nmr spectroscopy and molecular modeling methods. Two-dimensional nmr spectra, recorded in hexafluoroacetone/water, a mixture with structure stabilizing properties, showed an unusually high number of nuclear Overhauser effects, forming significative pattern to the drawing of a secondary structure. Conformations consistent with experimental NOE distances were obtained through molecular dynamics and energy minimization methods. These calculations yielded two stable conformers corresponding to an α-turn and a type III β-turn involving the last five C- terminal residues. Interestingly, the α-turn conformation was found to overlap with good agreement the crystallographic structure of the same fragment in the Gα(s) protein. (C) 2000 John Wiley and Sons, Inc. It has recently been reported that synthetic peptides corresponding to the C-terminal sequence of Gα, can be used to study the molecular mechanisms of interaction between this protein and G protein coupled receptors. A conformational analysis on a 11 amino acids peptides from the GαS C-terminus, GαS(384-394) (H-QRMHLRQYELL-OH), was performed by nmr spectroscopy and molecular modeling methods. Two-dimensional nmr spectra, recorded in hexafluoroacetone/water, a mixture with structure stabilizing properties, showed an unusually high number of nuclear Overhauser effects, forming significative pattern to the drawing of a secondary structure. Conformations consistent with experimental NOE distances were obtained through molecular dynamics and energy minimization methods. These calculations yielded two stable conformers corresponding to an α-turn and a type III β-turn involving the last five C-terminal residues. Interestingly the α-turn conformation was found to overlap with good agreement the crystallographic structure of the same fragment in the GαS protein.
Conformational studies on a synthetic C-terminal fragment of the alpha subunit of G(S) proteins.
D'URSI, Anna Maria;
2000-01-01
Abstract
It has recently been reported that synthetic peptides corresponding to the C-terminal sequence of Gα, can be used to study the molecular mechanisms of interaction between this protein and G protein coupled receptors (Hamm et al., Science, 1988, Vol. 241, pp. 832-835). A conformational analysis on a 11 amino acids peptide from the Gα(s) C-terminus, Gα(s)(384-394) (H- QRMHLRQYELL-OH), was performed by nmr spectroscopy and molecular modeling methods. Two-dimensional nmr spectra, recorded in hexafluoroacetone/water, a mixture with structure stabilizing properties, showed an unusually high number of nuclear Overhauser effects, forming significative pattern to the drawing of a secondary structure. Conformations consistent with experimental NOE distances were obtained through molecular dynamics and energy minimization methods. These calculations yielded two stable conformers corresponding to an α-turn and a type III β-turn involving the last five C- terminal residues. Interestingly, the α-turn conformation was found to overlap with good agreement the crystallographic structure of the same fragment in the Gα(s) protein. (C) 2000 John Wiley and Sons, Inc. It has recently been reported that synthetic peptides corresponding to the C-terminal sequence of Gα, can be used to study the molecular mechanisms of interaction between this protein and G protein coupled receptors. A conformational analysis on a 11 amino acids peptides from the GαS C-terminus, GαS(384-394) (H-QRMHLRQYELL-OH), was performed by nmr spectroscopy and molecular modeling methods. Two-dimensional nmr spectra, recorded in hexafluoroacetone/water, a mixture with structure stabilizing properties, showed an unusually high number of nuclear Overhauser effects, forming significative pattern to the drawing of a secondary structure. Conformations consistent with experimental NOE distances were obtained through molecular dynamics and energy minimization methods. These calculations yielded two stable conformers corresponding to an α-turn and a type III β-turn involving the last five C-terminal residues. Interestingly the α-turn conformation was found to overlap with good agreement the crystallographic structure of the same fragment in the GαS protein.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
