Nuclear pore complex

Nuclear pore complex
Diagram of the human cell nucleus with nuclear pores.
Schematic diagram of a nuclear pore complex within the nuclear envelope (1) with the outer ring (2), spokes (3), basket (4), and filaments (5).
Details
Identifiers
Latin	porus nuclearis
MeSH	D022022
TH	H1.00.01.2.01005
FMA	63148
Anatomical terminology [edit on Wikidata]

The nuclear pore complex (NPC), is a large protein complex giving rise to the nuclear pore. A great number of nuclear pores are studded throughout the nuclear envelope that surrounds the eukaryote cell nucleus. The pores enable the nuclear transport of macromolecules between the nucleoplasm of the nucleus and the cytoplasm of the cell. Small molecules can easily diffuse through the pores.^[1] Nuclear transport includes the transportation of RNA and ribosomal proteins from the nucleus to the cytoplasm, and the transport of proteins (such as DNA polymerase and lamins), carbohydrates, signaling molecules, and lipids into the nucleus. Each nuclear pore complex can actively mediate up to 1000 translocations per second.

The nuclear pore complex consists predominantly of a family of proteins known as nucleoporins (Nups). Each pore complex in the human cell nucleus is composed of about 1,000 individual protein molecules, from an evolutionarily conserved set of 35 distinct nucleoporins.^[2] The conserved sequences that code for nucleoporins regulate molecular transport through the nuclear pore.^[3][4] Nucleoporin-mediated transport does not entail direct energy expenditure but instead relies on concentration gradients associated with the RAN cycle (Ras-related nuclear protein cycle). In 2022 around 90% of the structure of the human NPC was elucidated in an open and a closed conformation, and published in a special issue of Science, featured on the cover.^[5][6][7] In 2024 the structure of the nuclear basket was solved, finalising the completion of the structure of the nuclear pore complex.^[8]

About half of the nucleoporins encompass solenoid protein domains, such as alpha solenoids or beta-propeller folds, and occasionally both as separate structural domains. Conversely, the remaining nucleoporins exhibit characteristics of "natively unfolded" or intrinsically disordered proteins, characterized by high flexibility and a lack of ordered tertiary structure. These disordered proteins, referred to as FG nucleoporins (FG-Nups), contain multiple phenylalanine–glycine repeats (FG repeats) in their amino acid sequences.^[9] FG-Nups is one of three main types of nucleoporins found in the NPC. The other two are the transmembrane Nups and the scaffold Nups. The transmembrane Nups are made up of transmembrane alpha helices and play a vital part in anchoring the NPC to the nuclear envelope. The scaffold Nups are made up of alpha solenoid and beta-propeller folds, and create the structural framework of NPCs.^[10]

The count of nuclear pore complexes varies across cell types and different stages of the cell's life cycle, with approximately 1,000 NPCs typically found in vertebrate cells.^[11] The human nuclear pore complex is a substantial structure, with a molecular weight of 120 megadaltons (MDa).^[12] Each NPC comprises eight protein subunits encircling the actual pore, forming the outer ring. Additionally, these subunits project a spoke-shaped protein over the pore channel. The central region of the pore may exhibit a plug-like structure; however, its precise nature remains unknown, and it is yet undetermined whether it represents an actual plug or merely cargo transiently caught in transit.