Download citation
Acta Cryst. (2014). A70, C417
Download citation

link to html
Retromer is a peripheral membrane protein complex that plays a critical role in a broad range of physiological, developmental and pathological processes including Wnt signalling, toxin transport and amyloid production in Alzheimer's disease. The classical mammalian retromer complex consists of a core heterotrimeric cargo recognition sub-complex (VPS26, VPS29 and VPS35) associated with a dimer of proteins from the SNX–BAR sorting nexin family that drives membrane deformation and tubulation. By recruiting the cargo-selective sub-complex to the forming tubules, the SNX–BAR coat complex mediates the retrograde transport of proteins from endosomes to the trans-Golgi network. Recent studies, however, have highlighted the molecular and functional diversity of retromer and the identification of new interacting proteins has revealed that the role of retromer extends to aspects of endosome-to-plasma membrane sorting and regulation of signalling events. Emerging evidence indicates that cargo specificity is mediated by specific sorting nexins. These include SNX3, involved in the trafficking of the Wntless/MIG-14 protein, and SNX27, a PX-FERM protein that mediates the retrieval of the β2-adrenergic receptor.Using the MX and SAXS/WAXS beamlines at the Australian Synchrotron, we have acquired crystallographic and small angle scattering data to determine how the core cargo recognition sub-complex assembles and to characterise the retromer-associated sorting nexins. We are using this structural information in combination with biochemical and biological studies in a synergistic approach to understand retromer-mediated endosomal protein sorting and how this fascinating protein complex contributes to a diverse set of cellular processes. The retromer complex is conserved across all eukaryotes. We are also currently exploring the structure of these proteins in the thermophilic fungus Chaetomium thermophilum and initial crystallisation experiments have produced some promising results.
Follow Acta Cryst. A
Sign up for e-alerts
Follow Acta Cryst. on Twitter
Follow us on facebook
Sign up for RSS feeds