Boundary Issues

Compartmentalization is essential for most biological processes. Yet, selective permeability of biological boundaries matters. For many cellular processes, ions, small molecules, peptides, RNAs, and large multicomponent complexes must be able to transit across membranes and perturbation of this exchange can cause disease. The challenge is how to preserve a boundary while still allowing necessary commerce across it. In eukaryotic cells, organelles define regions where distinct biochemical processes can take place. For example, separation of the nucleus from the cytoplasm enables complex layers of gene expression regulation, but for this towork,molecules need to both enter and exit the nucleus. The nuclear pores that stud the envelope provide the thoroughfares for this exchange. But nuclear pores are not mere holes; these protein complexes allow selective transport of entities larger than about 40 kDa across the nuclear envelope. In the last few years, advances in structural biology and the adoption of integrative methods that marry structural, biochemical, and physical data have revealed much about the proteins and subcomplexes that comprise the pore. Two recent papers in Science provide a picture of the pore’s membraneembedded core, defining the majority of this monumental scaffold (Kosinski et al., 2016; Lin et al., 2016). Using different types of data in integrative approaches, each reveals an 8-fold spoke-like architecture for the inner core. Early model building, alongside comparatively low-resolution structural approaches, suggested that the nuclear pore consists of two planes of stacked rings spanning the membrane. The new structures reveal amore complex ring architecture building and buttressing the pore. With this safe surround, like the walls of a tunnel, transport can occur, and these new nearatomic composite structures bring uscloser to understanding how this massive entity is assembled and stabilized. The true channel for molecular exchange, termed the diffusion barrier, remains something of a conundrum. The diffusion barrier allows free passage of small moieties, but transport of sizeable cargo requires interaction of certain nu-