Molecular evolution of NPY receptor subtypes

Receptor Subtype-specific Docking of Asp6.59 with C-terminal Arginine Residues in Y Receptor Ligands

“…Evolutionary and structural comparison studies suggest that Y 1 R and Y 4 R form a distinct subfamily of YRs, and Y 2 R and Y 5 R orthologs showed closer structural relation to each other than to members of the Y 1 R/Y 4 R subfamily (13). This is in good agreement with the identified differences in the binding mode of the ligand.…”

“…The effects of NPY, PYY, and PP are transmitted by at least five rhodopsinlike GPCRs named Y 1 receptor (Y 1 R), Y 2 R, Y 4 R, Y 5 R, and y 6 R. The y 6 R shows a restricted genomic presence, indicated by the lowercase letter, being functionally expressed in rabbits and mice but is truncated in humans and absent in rat (9 -11). Y 1 R, Y 4 R, and y 6 R can be combined to a subfamily sharing ϳ50% overall amino acid identity with each other but only 27-31% with Y 2 R and Y 5 R (12,13). Despite the low sequence similarity between YR subtypes, all bind the same family of peptides.…”

“…Y 1 R and Y 4 R require the complete N terminus of the ligand (15,19,20). Y 5 R accepts peptides with the deletion of the first amino acid (21), and Y 2 R even binds significantly shorter peptides (NPY ) or centrally truncated analogs ([Ahx [5][6][7][8][9][10][11][12][13][14][15][16][17][18][19][20][21][22][23][24] ]NPY) with only minor effects on affinity (19,22). However, the C-terminal pentapeptide of all natural ligands was identified as an essential region for binding to all YRs (23,24), and these residues of the ligand C terminus seem to represent a core contact domain.…”

Evidence for the Existence of an Additional Class of Neuropeptide Y Receptor Sites in Rat Brain

“…Specific sites characterized in the present study clearly displayed high affinities for both PYY and PPs, excluding the Y 3 subtype as the one characterized here. It is noteworthy that elaborated phylogenic studies suggested the existence of additional NPY receptor subtypes, in fact up to eight to nine subtypes in total (Larhammar, 1996;Larhammar and Salaneck, 2004).…”

Peptide YY3-36 Decreases Reinstatement of High-Fat Food Seeking during Dieting in a Rat Relapse Model

“…PYY3-36 has high affinity for neuropeptide Y (NPY) Y2 receptors and lower affinity for Y1 and Y5 NPY receptors (Grandt et al, 1992;Ballantyne, 2006); NPY is a hypothalamic peptide that increases food intake after hypothalamic or ventricular injections (Leibowitz, 1995). The Y2 receptor is a putative NPY presynaptic inhibitory autoreceptor, whereas Y1 and Y5 are postsynaptic excitatory receptors (Wahlestedt et al, 1986;Larhammar and Salaneck, 2004). Systemic PYY3-36 injections decrease food intake in mice, rats, monkeys, and humans (Batterham et al, 2002(Batterham et al, , 2003Moran et al, 2005;Chelikani et al, 2006) [but see Tschop et al (2004) and Boggiano et al (2005) for different results].…”