Nuclear Pore Complex Structure and Transport Mechanism

Nuclear Pore Complex (NPC) Structure and Function

NPC as Gatekeepers

Embedded within the nuclear envelope are nuclear pore complexes (NPCs), large protein structures situated in circular openings where the inner and outer nuclear membranes fuse. These aqueous protein channels regulate the transport of proteins and RNA across the nuclear envelope, acting as gatekeepers of the nucleus and facilitating nearly all transport between the nucleoplasm and cytoplasm.

NPC Architecture

The main NPC structure features rings on both the cytoplasmic and nucleoplasmic sides, with a luminal ring (LR) in between, creating twofold symmetry across the nuclear membrane.

Transport Across the Nuclear Envelope

Selective Permeability

While small molecules like metabolites and ions can freely cross the nuclear envelope, larger macromolecules (proteins, mRNA, tRNA, ribosome subunits, and viruses) require active transport through the NPC. Each macromolecule type has a specific transport mechanism.

Protein Import and Export

Protein transport across the nuclear membrane is regulated by interactions between protein cargo, nuclear transport receptors (NTRs, such as importins, exportins, transportins, and karyopherins), and the small GTPase Ran. Ran modulates the ability of importins and exportins to carry their cargo.

Nuclear Localization Signal (NLS)

For active transport through the NPC, a protein must possess a nuclear localization signal (NLS) sequence. Recognition of the NLS by the adaptor protein importin-α is the first step in import complex assembly. This is followed by binding of the karyopherin importin-β, forming a trimeric import complex. Importin-β acts as the transport factor, carrying the cargo through the NPC. In cases of atypical NLSs, importin-β binds directly to the cargo. The NTRs, through direct or indirect interaction with the NLS, determine which cargo can pass through the nuclear pore.

Import Complex Disassembly and Recycling

Upon entering the nucleus, RanGTP binds to importin-β, releasing the cargo. The importin-β–RanGTP complex returns to the cytosol, where GTP hydrolysis disassembles it for the next import cycle. The dynamic equilibrium of the import complex within the pore ensures a net flow of cargo towards the nucleoplasm.