Conformational studies on a synthetic C-terminal fragment of the alpha subunit of G(S) proteins.
It has recently been reported that synthetic peptides corresponding to the C-terminal sequence of G alpha, 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 G alpha(S) C-terminus, G alpha(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 alpha-turn and a type III beta-turn involving the last five C-terminal residues. Interestingly, the alpha-turn conformation was found to overlap with good agreement the crystallographic structure of the same fragment in the G alpha(S) protein.
Albrizio
S
S
Dipartimento di Scienze Farmaceutiche, Università di Salerno, Piazza V. Emanuele 9, 84084 Penta di Fisciano, Salerno, Italy.
D'Ursi
A
A
Fattorusso
C
C
Galoppini
C
C
Greco
G
G
Mazzoni
M R
MR
Novellino
E
E
Rovero
P
P
D000595:Amino Acid Sequence; D003198:Computer Simulation; D019205:GTP-Binding Protein alpha Subunits, Gs / Q000138:chemical synthesis / Q000737:chemistry*; D009682:Magnetic Resonance Spectroscopy; D008958:Models, Molecular; D010446:Peptide Fragments / Q000138:chemical synthesis / Q000737:chemistry*; D011487:Protein Conformation
D010446:Peptide Fragments; D019205:GTP-Binding Protein alpha Subunits, Gs