Akademik Veri Yönetim Sistemi
49th FEBS Congress, İstanbul, Türkiye, 5 - 09 Temmuz 2025, ss.180, (Özet Bildiri)
The neuropeptide Y receptor family, which belongs to the ClassA (Rhodopsin-like) group of the G-protein coupled receptor(GPCR) family, plays a significant role in regulating neurologicaland psychiatric disorders, pain management, anxiety, depression,migraines, and certain cardiovascular diseases.1,2 So far, 4 typesof receptors from this family (Y1, Y2, Y4, Y5) have been clonedfrom humans2 , and only the 3D structure of the Y5 receptor isnot available in databases. However, although the NeuropeptideY receptor family members are generally similar to each other,there is a difference of 64 amino acids in NPY5R, some of whichare in the intracellular region and others in the extracellularregion. The impact of this difference on the Gi,o protein couplingdomain and the mechanisms of agonistic/antagonistic bindingremains unknown, and research in this area is limited. Therefore,in this study, we performed molecular dynamics simulations byembedding the Y5 receptor-GPCR complex into the cellmembrane to better understand these aspects. To determine the3D structure of the NPY5 receptor, we also applied homologymodeling methodology. Based on preliminary results from MDsimulations, the loop structure (IL3), which contains a helix andconnecting TM5 to TM6 of the receptor, as well as the NPxxYmotif in TM7 of the receptor, were found to interact with thealpha subunit of the G i,o protein. While this interaction ismaintained in the presence of an agonist, a counterclockwise movement of the beta and gamma subunits occurs in the absenceof an agonist. References 1. Nelson TY et al. (2024) ACSPharmacol Transl Sci. 7 (12), 3718-3728 2. Pedragosa-Badia Xet al. (2013). Front Endocrinol (Lausanne). 4(FEB):1-13.