The retromer complex regulates retrograde protein trafficking of receptor proteins from the endosome to the trans-Golgi network. The retromer complex consists of two functional sub-complexes, a membrane-deforming subunit (Sorting nexins (SNX1/2 and SNX5/6 or SNX3) and a cargo selective adaptor subunit (VPS26, VPS35 and VPS29).
SNX has a PX domain that interacts with phosphatidylinositol 3-phosphates present on the membranes and a banana-shaped BAR domain that helps to curve membranes. There is no lipid binding domain in the cargo selective adaptor subunit. A small GTPase Rab7 and Rab GTPase-activating proteins, TBC1D5 might be required for the recruitment of this adaptor subunit (VPS26, VPS35 and VPS29) on endosomes.
By the combined use of X-ray protein crystallography and other biophysical methods, we aim to understand the molecular mechanisms of endosomal retrograde protein trafficking.