Human APG1 gene is homologous to Drosophila methuselah gene associated with extended life span. A peptide (APG1: RNGKRSNRTLREE) corresponding to a predicted region of the intracellular third loop of G protein-coupled receptor coded in human APG1 gene could activate G(i) protein alpha subunit directly. The three-dimensional molecular structure of the peptide in SDS-d(25) micelles was determined by 2D H-1 NMR spectroscopy. APG1 formed an alpha-helical structure at the C-terminal site and a positive charge cluster at the N-terminal site. The cluster was also found in several other G(i) protein-coupled receptor peptides. Therefore, the positive charge cluster on the helical structure might be engaged in G protein activation. (c) 2006 Elsevier Inc. All rights reserved.