The Structure and Function of the Nuclear Pore Complex Michael Rexach, MCD Biology Our work centers on elucidating the structure and function of the nuclear pore complex (NPC). This is the supramolecular porin structure in the nuclear envelope of all eukaryotes that creates the aqueous channel connecting the cytoplasm and nucleoplasm of the cell. Its main function is to serve as a size-selective gate in the vital flow of macromolecules between these compartments. It is composed of proteins termed nucleoporins, and approximately 450 of them are needed to form each NPC. Molecular Interactions at the Nuclear Pore Complex We have discovered that a defined subset of nucleoporins are natively unfolded (intrinsically disordered), yet can interact with each other to form a quaternary structure held together by weak hydrophobic attractions. Indeed, this network of FG domains functions in vivo as the physical element of the size-selective diffusion barrier in the NPC. We are currently characterizing the dynamic behavior of these natively unfolded nucleoporins and their structural arrangement within the NPC transport conduit using combination of NMR spectroscopy and molecular modeling, guided by an extensive evolutionary analysis of the nucleoporin family in four Saccharomyces strains.