Characterizing the molecular interactions between Y receptors and arrestin (A04)

• Subject Area: Biochemistry ; Biophysics ; Structural Biology ; Cell Biology
• Term: since 2020
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 421152132

We investigate the interaction between neuropeptide Y receptors (YRs) and arrestin with the focus on dynamic aspects of the receptors and their interaction with arrestin in the biological membrane environment. To achieve this, we will (i) combine peptide synthesis and protein ligation techniques to prepare NMR-active proteins with isolated isotopic labels and EPR-active proteins. (ii) We will use solution and solidstate NMR techniques to determine the backbone structure of segments of arrestin in interaction with YRs. (iii) We will analyze the dynamics of the interaction and verify essential interaction partners with mutagenesis of both arrestin and YRs. (iv) Furthermore, we will investigate the molecular dynamics of the YRs in response to agonist and arrestin binding as well as dynamic alterations in response to conformational changes arrestin undergoes upon binding to the receptor.

• DFG Programme: Collaborative Research Centres
• Subproject of: SFB 1423: Structural Dynamics of GPCR Activation and Signaling
• Applicant Institution: Universität Leipzig
• Project Heads: Professorin Dr. Annette G. Beck-Sickinger; Professor Dr. Daniel Huster