Pancreatic polypeptide is recognized by two hydrophobic domains of the human Y4 receptor binding pocket.

ABSTRACT: Structural characterization of the human Y4 receptor (hY4R) interaction with human pancreatic polypeptide (hPP) is crucial, not only for understanding its biological function but also for testing treatment strategies for obesity that target this interaction. Here, the interaction of receptor mutants with pancreatic polypeptide analogs was studied through double-cycle mutagenesis. To guide mutagenesis and interpret results, a three-dimensional comparative model of the hY4R-hPP complex was constructed based on all available class A G protein-coupled receptor crystal structures and refined using experimental data. Our study reveals that residues of the hPP and the hY4R form a complex network consisting of ionic interactions, hydrophobic interactions, and hydrogen binding. Residues Tyr(2.64),

SUBMITTER: Pedragosa-Badia X 

PROVIDER: S-EPMC3937655 | biostudies-literature | 2014 Feb

REPOSITORIES: biostudies-literature