Sohail Mahmood

Canada

Role of glucocorticoid receptor and macrophage polarization in anxiety disorder

Delina Fess, Sohail Mahmood

Abstract

Background

Introduction: E-Cadherin is a key cell adhesion molecule involved in mediating cell-cell interactions with the inhibitory receptor KLRG-1, which is a process crucial for regulating immune responses and maintaining tissue integrity (Nakamura et al., 2009). To investigate the binding specificity at the E-Cadherin-KLRG-1 interface, we focused on the active site characterized by the peptide sequence QVFLSEAF. In other words, we hypothesize that peptides lacking these critical amino acids in their active sites will exhibit significantly reduced binding, or no binding at all. We designed and synthesized a comprehensive library of peptide variants by systematically substituting each amino acid in this sequence,
creating 136 different possibilities of potential binding mimics on the E-Cadherin protein surface.

Methods

Methods: Using Pepsite, for spatial position specific scoring computationally, we evaluated these synthetic binding sites and visualized the interactions with KLRG-1. Our hypothesis is that these synthetic peptides will successfully bind to KLRG-1, given that they are one of the iterations of an existing active site known for its binding capacity using python to create a computational assistive tool for Pepsite.

Results

Results/Discussion: Our analysis revealed that the randomly selected peptide variants demonstrated binding affinity to the KLRG-1 docking site, confirming our hypothesis that these peptides, based on their active site substitutions, effectively bind to the receptor.

Conclusions

This study not only provides insights into the key determinants of E-Cadherin interactions with KLRG-1 but also provides a framework for the design of synthetic novel peptides with potential therapeutic applications in modulating immune responses.

References: Nakamura, S., Kuroki, K., Ohki, I., Sasaki, K., Kajikawa, M., Maruyama, T., Ito, M., Kameda, Y., Ikura, M., Yamamoto, K., Matsumoto, N., & Maenaka, K. (2009). Molecular basis for E-cadherin recognition by killer cell lectin-like receptor G1 (KLRG1). Journal of Biological Chemistry, 284(40), 27327-27335.https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2785660/