Nucleoporin

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Nucleoporin 133/155, N terminal
SCOP2
1XKS / SCOPe / SUPFAM
Available protein structures:
Pfam  structures / ECOD  
PDBRCSB PDB; PDBe; PDBj
PDBsumstructure summary
Nucleoporin 133/155, C terminal (ACE2)
NUP133 (this domain; right) interacting with NUP107 (PDB 3CQC).
Identifiers
SymbolNucleoporin_C
PfamPF03177
InterProIPR007187
Available protein structures:
Pfam  structures / ECOD  
PDBRCSB PDB; PDBe; PDBj
PDBsumstructure summary
PDB3I4R
FG repeat
Identifiers
SymbolNucleoporin_FG
PfamPF13634
Pfam clanCL0647
InterProIPR025574
Available protein structures:
Pfam  structures / ECOD  
PDBRCSB PDB; PDBe; PDBj
PDBsumstructure summary

Nucleoporins are a family of proteins which are the constituent building blocks of the

Nucleoporin 62 is the most abundant member of this family.[2] Nucleoporins are able to transport molecules across the nuclear envelope at a very high rate. A single NPC is able to transport 60,000 protein molecules across the nuclear envelope every minute.[3]

Structure

Nucleoporins aggregate to form a

nuclear pore complex, an octagonal ring that traverses the nuclear envelope. The ring consists of eight scaffold sub-complexes, with two structural layers of COPII-like coating sandwiching some proteins that line the pore. From the cytoplasm to the nucleoplasm, the three layers of the ring complex is named the cytoplasm, inner pore, and nucleoplasm rings respectively. Different sets of proteins associate on either ring, and some transmembrane proteins anchor the assembly to the lipid bilayer.[4]

In a scaffold subcomplex, both the cytoplasm and the nucleoplasm rings are made up of Y-complexes, a protein complex built out of, among others, NUP133 and NUP107. On each end of each of the eight scaffolds are two Y-complexes, adding up to 32 complexes per pore.[4] The relationship of the membrane curvature of a nuclear pore with Y-complexes can be seen as analogous to the budding formation of a COPII coated vesicle.[3] The proteins lining the inner pore make up the NUP62 complex.[4]

On the nucleoplasm side, extra proteins associated with the ring form "the nuclear basket", a complex capable of tethering the nucleoporin to the nuclear lamina and even to specific parts of the genome.[4] The cytoplasmic end is less elaborate, with eight filaments projecting into the cytoplasm. They don't seem to have a role in nuclear import.[5]

Some nucleoporins contain FG repeats. Named after

hydrophilic amino acids. These flexible parts form unfolded, or disordered segments without a fixed structure.[6] They form a mass of chains which allow smaller molecules to diffuse through, but exclude large hydrophilic macromolecules. These large molecules are only able to cross a nuclear pore if they are accompanied by a signaling molecule that temporarily interacts with a nucleoporin's FG repeat segment. FG nucleoporins also contain a globular portion that serves as an anchor for attachment to the nuclear pore complex.[3]

Membrane nucleoporins associate with both the scaffold and the nuclear membrane. Some of them, like

GP210, cross the entire membrane, others (like NUP98) act like nails with structural parts for the lining as well as parts that punch into the membrane.[4] NUP98 was previously thought to be an FG nucleoporin, until it was demonstrated that the "FG" in it have a coiled-coil fold.[4]

Nucleoporins have been shown to form various subcomplexes with one another. The most common of these complexes is the nup62 complex, which is an assembly composed of

kinetochores and plays a role in mitosis.[8]

Evolution

Many structural nucleoporins contain solenoid protein domains, domains consisting of repeats that can be stacked together as bulk building blocks. There are beta-propeller domain with similarities to WD40 repeats, and more interestingly, unique types of alpha solenoid (bundles of helixes) repeats that form a class of their own, the ancestral coatomer elements (ACE). To date, two classes of ACEs have been identified. ACE1 is a 28-helix domain found in many scaffolding nucleoproteins as well as SEC31, a component of COPII. ACE2, shown in the infobox, is found in yeast Nup157/Nup170 (human Nup155) and Nup133. In either case, the shared domains, like their names suggest, indicate a shared ancestry both within nucleoproteins and between nucleoproteins and cotamers.[9]

All living eukaryotes share many important components of the NPC, indicating that a complete complex is present in their common ancestor.[10]

Function

Nucleoporins mediate transport of

transcription.[13] Depending on their function, certain nucleoporins are localized to either the cytosolic or nucleoplasmic side of the nuclear pore complex. Other nucleoporins may be found on both sides. It has been recently shown that FG nucleoporins have specific evolutionary conserved features encoded in their sequences that provide insight into how they regulate the transport of molecules through the nuclear pore complex.[14][15]

Transport mechanism

Nucleoporins regulate the transport of macromolecules through the

GDP and has the ability to change a karyopherin's affinity for its cargo. Inside the nucleus, RanGTP causes an importin karyopherin to change conformation, allowing its cargo to be released. RanGTP can also bind to exportin karyopherins and pass through the nuclear pore. Once it has reached the cytosol, RanGTP can be hydrolyzed to RanGDP, allowing the exportin's cargo to be released.[16]

Pathology

Several diseases have been linked to pathologies of nucleoporins, notably

tumors
.

Nucleoporins have been shown to be highly sensitive to

nucleoporin 62.[2]

primary biliary cirrhosis which destroys the bile ducts of the liver.[7]

Decreases in the production of the p62 complex are common to many

neurodegenerative diseases. Modification of the p62 promoter by oxidation is correlated with Alzheimer's disease, Huntington's disease, and Parkinson's disease among other neurodegenerative disorders.[17]

Increased expression of the

neoplasms.[18]

Nucleoporin protein aladin is a component of the nuclear pore complex. Mutations in the aladin gene are responsible for triple-A syndrome, an autosomal recessive neuroendocrinological disease. Mutant aladin causes selective failure of nuclear protein import and hypersensitivity to oxidative stress.[19] The import of DNA repair proteins aprataxin and DNA ligase I is selectively decreased, and this may increase the vulnerability of the cell's DNA to oxidative stress induced damages that trigger cell death.[19]

Examples

Each individual nucleoporin is named according to its molecular weight (in kilodaltons). Below are several examples of proteins in the nucleoporin family:

References

  1. PMID 9159086
    .
  2. ^
    PMID 10926833
    .
  3. ^
    ISBN 978-1-4292-3413-9
    .
  4. ^
    S2CID 35394962
    . Retrieved 10 April 2019.
  5. PMID 12105182
    .
  6. PMID 12604785
    .
  7. ^
    PMID 12753810
    .
  8. PMID 15146057
    .
  9. PMID 19674973
    .
  10. PMID 20949036
    .
  11. PMID 12543930
    .
  12. PMID 16739728
    .
  13. PMID 20977914
    .
  14. PMID 26541386
    .
  15. PMID 24066078
    .
  16. PMID 8923203
    .
  17. PMID 19481605
    .
  18. ^ "Entrez Gene: NUP88 nucleoporin 88kDa"
  19. ^
    PMID 16467144
    .

External links
Retrieved from "https://en.wikipedia.org/w/index.php?title=Nucleoporin&oldid=1187424876"