From Prediction to Discovery: Leveraging AlphaFold to Characterise SNX27 and Its Interactions

Speaker: Dr Qian Guo. Postdoctoral Research Fellow at the Institute for Molecular Bioscience
Date: Thursday July 30 1pm – 2pm AEST
Zoom: Click here to join the seminar

Abstract:
Learn how AI and Alphafold have advanced from basic protein structural predictions to increasingly in-depth integrative analyses.

Endosomal protein sorting is essential for maintaining cellular homeostasis by regulating the trafficking and recycling of transmembrane proteins. Central to this process is the Retromer complex, which coordinates cargo retrieval together with sorting nexin (SNX) adaptors, including SNX27. The recent development of AlphaFold has fundamentally transformed structural biology by enabling rapid and accurate prediction of protein complexes, accelerating the discovery of previously unrecognised molecular interactions.

In this seminar, I will present how AlphaFold-guided structural biology has advanced our understanding of the SNX27-mediated endosomal trafficking pathway. By integrating AlphaFold predictions with biochemical assays, X-ray crystallography, and cellular validation, we have characterised the molecular basis of SNX27 interactions with multiple classes of binding partners. These include BAR domain-containing sorting nexins (SNX1 and SNX2), the WASH complex component FAM21, and a newly identified group of non-canonical PDZ-binding proteins. I will also discuss recent work demonstrating how AlphaFold, combined with proximity proteomics and structural validation, uncovered direct interactions between the Retromer complex and Rab regulators, revealing an unexpected role for Retromer as a coordinator of Rab GTPase activity in addition to its established function in cargo recycling.

Together, these studies illustrate how AI-guided structural prediction, combined with rigorous experimental validation, is transforming the way we generate biological hypotheses and discover new mechanisms of membrane trafficking. This work highlights the power of AlphaFold not only as a structure prediction tool, but also as a catalyst for biological discovery.

Bio:

Dr Qian Guo is a Postdoctoral Research Fellow at the Institute for Molecular Bioscience, The University of Queensland. Her research focuses on the molecular mechanisms of endosomal trafficking, integrating structural biology, biochemistry and cell biology to understand how the Retromer complex and sorting nexins regulate membrane protein recycling. She completed her PhD under Professor Brett Collins and is currently a postdoctoral researcher in Professor Jennifer Stow’s lab. Today, she will discuss how AlphaFold has accelerated the discovery of novel protein interactions and transformed structural biology research.