A physical model describing the interaction of nuclear transport receptors with FG nucleoporin domain assemblies

The cells of animals, plants and other eukaryotic organisms contain a compartment called the nucleus that contains most of the cell's genetic material. Proteins and other molecules – collectively known as cargos – can enter and exit the nucleus via tiny channels in the membrane that surrounds and protects it. Receptor proteins – called nuclear transport receptors – bind to potential cargos and shuttle them through the channels. This selective transport process relies on the nuclear transport receptors being attracted to flexible, spaghetti-like proteins that are anchored to the walls on the inside of each channel. However, because of their flexible and disordered nature, these so-called FG domains are difficult to study, and the details of the transport process are poorly understood. Zahn, Osmanovic et al. decided to study how the FG domains behave and what happens when they interact with nuclear transport receptors by using ultrathin films made of just the FG domains. This is a good model system because the films are easier to study than the whole channels, but are likely to retain the essential properties of the real barrier formed in the nuclear envelope. Zahn, Osmanovic et al. compared the binding of two nuclear transport receptors of different sizes, taken from humans and yeast, to FG domain films made from one of three different FG domains. The experiments showed that the different nuclear transport receptors bind to the different FG domains in very similar ways. Zahn, Osmanovic et al. then used a computational model that essentially represented the FG domains as sticky spaghetti and the nuclear transport receptors as perfectly round meatballs. This sticky-spaghetti-with-meatballs model reproduced the experimental data, implying that the exact chemical make-up and structure of the molecules may not be critical for controlling the transport of cargo across the nuclear envelope. Future studies will test whether the generic physical features of nuclear transport receptors and FG domains can indeed explain how the cargo molecules pass through the nuclear envelope.