Probing and modulating the function of the retromer endosomal trafficking complex through novel macrocyclic peptides
01 Sep 2022

The evolutionarily conserved Retromer complex is a vital regulator responsible for endosomal membrane trafficking. Its dysfunction is linked to neurodegenerative disease.

A random nonstandard peptides integrated discovery (RaPID) approach was employed to identify a group of macrocyclic peptides that bind retromer with high affinity and can be divided into two categories: retromer stabilizers or protein interaction inhibitors. Using a combination of mass photometry, cryo-EM and X-ray crystallography stabilizing peptides can act as molecular chaperones of retromer with minimal disruption to its accessory protein interactions. Meanwhile, the inhibitors act by structurally mimic endogenous interacting proteins.

In this webinar, find an explanation on how the macrocyclic peptides can be used as a novel toolbox to study retromer-mediated endosomal trafficking and for therapeutic targeting of retromer function. Highlighted, is the method mass photometry, which enables characterization of protein complexes.

Key learning objectives

  • An understanding of the RaPID approach for drug discovery, as applied to macrocyclic peptides that bind to retromer
  • Insights into therapeutic targeting of retromer-dependent disease pathways and novel ways to study retromer function
  • An understanding of how mass photometry can be used to probe complex formation and characterize proteins

Who should attend?

Anyone interested in structural biology, membrane trafficking, mass photometry, and novel drug-discovery approaches.

Certificate of attendance

All webinar participants can request a certificate of attendance, including a learning outcomes summary, for continuing education purposes.