Our research interest is focused on intracellular trafficking processes. Eukaryotic cells have elaborate mechanisms of protein transport through vesicular trafficking. The Golgi is the major compartment at which different sorting pathways diverge. Here, proteins undergo final modifications before being directed into a variety of carrier vesicles for transport to the cell surface, endosomal compartments or lysosomes. Vesicle targeting and fusing with an acceptor membrane are regulated by a variety of integral and peripheral membrane proteins that are highly conserved. While fusion between vesicles is critical in pairing of integral membrane SNARE proteins, peripheral multi-protein tethering complexes act upstream by selecting and tethering target membranes in long-range interaction. My current research is focused on developing an understanding, on the atomic level, of how tethering complexes contribute to specificity of membrane fusion by recognizing vesicle features on both donor and acceptor membranes. To pursue these studies I use X-ray crystallography of protein complexes in combination with cell biology and biochemistry. Since vesicle tethering events play key roles in intracellular network, studying tethering factors from a structural viewpoint represents a crucial stage in understanding how protein-protein recognition and protein-membrane interactions regulate the correct vesicle targets. Many clinical manifestations of diseases are related to malfunction or hijacking of these pathways, therefore detailed knowledge of these interactions is necessary to search for possible therapies.
Hierro A, Rojas AL, Rojas R, Murthy N, Effantin G, Kajava AV, Steven AC, Bonifacino JS, Hurley JH; Functional architecture of the retromer cargo-recognition complex. Nature 25, 449 1063-1067 (2007)