Recently, the research paper entitled Structural basis for the tethered peptide activation of adhesion GPCRs by Dr. Zhang Daolai from the G protein-coupled receptors and drug development team of the School of Pharmacy (School of Wine) was published online in Nature.
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The adhesion receptors GPR133 and GPR114 were used as models for structural analysis to explore the mechanisms of aGPCR activation by Stachel sequences (Figure 1). It was found that the GPR133GPS undergoes hydrolysis and NTF-CTF separation on the plasma membrane, while GPR114 does not undergo autohydrolysis and can sense mechanical force. In addition, it was proved by functional experiments that the receptors were activated by the Stachel sequences after sensing mechanical force (Figure 2). The cryogenic electron microscopy (cryo-EM) structures analysis further confirmed that the conserved HIM (Fss-03xφφφxφss-09) composed of five hydrophobic amino acids in Stachel plays a central role in the interaction between Stachel sequences and receptors (Figure 3). It is clarified that the structural basis for the recognition of Stachel sequences by receptors, reveals the activation mechanism of adhesion receptors under the action of mechanical force depending on Stachel sequences, and provides insights into the aGPCR and G protein coupling mediated by Stachel sequences receptor. It also provides a basis for the design of exogenous short peptides with Stachel sequences.
Prof. Sun Jinpeng of Shandong University is the corresponding author of the paper, and the School of Basic Medicine of Shandong University is the first author institute. Dr. Zhang Daolai from the G protein-coupled receptors and drug development team of the School of Pharmacy (School of Wine) of our school undertook part of the research work and participated in the publication of the paper as a co-author. The publication of this paper has a positive effect on further strengthening the discipline construction of our school and improving our school's ESI global ranking.
Article Link:
https://www.nature.com/articles/s41586-022-04619-y
SOURCE: School of Pharmacy (School of Wine)
BY: Zhang Daolai
