Nanoscale stiffness topography reveals structure and mechanics of the transport barrier in intact nuclear pore complexes.

The nuclear pore complex (NPC) is the gate for transport between the cell nucleus and the cytoplasm. Small molecules cross the NPC by passive diffusion, but molecules larger than ∼5 nm must bind to nuclear transport receptors to overcome a selective barrier within the NPC. Although the structure and shape of the cytoplasmic ring of the NPC are relatively well characterized, the selective barrier is situated deep within the central channel of the NPC and depends critically on unstructured nuclear pore proteins, and is therefore not well understood.

Heat shock protein 90 controls HIV-1 reactivation from latency.

Latency allows HIV-1 to persist in long-lived cellular reservoirs, preventing virus eradication. We have previously shown that the heat shock protein 90 (Hsp90) is required for HIV-1 gene expression and mediates greater HIV-1 replication in conditions of hyperthermia. Here we report that specific inhibitors of Hsp90 such as 17-(N-allylamino)-17-demethoxygeldanamycin and AUY922 prevent HIV-1 reactivation in CD4+ T cells.

Cohesiveness tunes assembly and morphology of FG nucleoporin domain meshworks - Implications for nuclear pore permeability.

Nuclear pore complexes control the exchange of macromolecules between the cytoplasm and the nucleus. A selective permeability barrier that arises from a supramolecular assembly of intrinsically unfolded nucleoporin domains rich in phenylalanine-glycine dipeptides (FG domains) fills the nuclear pore. There is increasing evidence that selective transport requires cohesive FG domain interactions.

Viruses challenge selectivity barrier of nuclear pores.

Exchange between the nucleus and the cytoplasm occurs through nuclear pore complexes (NPCs) embedded in the double membrane of the nuclear envelope. NPC permeability barrier restricts the entry of inert molecules larger than 5 nm in diameter but allows facilitated entry of selected cargos, whose size can reach up to 39 nm. The translocation of large molecules is facilitated by nuclear transport receptors (NTRs) that have affinity to proteins of NPC permeability barrier.

Systematic analysis of barrier-forming FG hydrogels from Xenopus nuclear pore complexes.

Nuclear pore complexes (NPCs) control the traffic between cell nucleus and cytoplasm. While facilitating translocation of nuclear transport receptors (NTRs) and NTR·cargo complexes, they suppress passive passage of macromolecules 30 kDa. Previously, we reconstituted the NPC barrier as hydrogels comprising S.

The permeability of reconstituted nuclear pores provides direct evidence for the selective phase model.

Nuclear pore complexes (NPCs) maintain a permeability barrier between the nucleus and the cytoplasm through FG-repeat-containing nucleoporins (Nups). We previously proposed a "selective phase model" in which the FG repeats interact with one another to form a sieve-like barrier that can be locally disrupted by the binding of nuclear transport receptors (NTRs), but not by inert macromolecules, allowing selective passage of NTRs and associated cargo. Here, we provide direct evidence for this model in a physiological context.