Enzymology of autoproteolysis and signaling function of the GAIN domain in adhesion GPCRs (A06)

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

The continued aim of this project is to understand the basis of the structural dynamics of the GAIN domain, the defining structural element of all adhesion GPCRs. We will focus on GAIN domain autoproteolytic activity, and release of the Stachel sequence for binding to the 7TM domain. Previous work led to the hypothesis that several GPS-distant elements of the GAIN domain impact self-cleavage, including the mostly conserved direct environment of the GPS motif, residues of the more flexible and diverse flap regions in at the domain’s surface, structural components of the 7TM domain, and molecules that assist with GAIN domain folding. We investigate each of these classes of contributing factors to aGPCR self-cleavage and Stachel release to obtain a deeper understanding of the unique role of the GAIN domain and its self-cleavage in aGPCR synthesis, trafficking and signalling.

• DFG Programme: Collaborative Research Centres
• Subproject of: SFB 1423: Structural Dynamics of GPCR Activation and Signaling
• Applicant Institution: Universität Leipzig
• Project Heads: Professor Dr. Tobias Langenhan; Professor Dr. Norbert Sträter