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From Proteopedia
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NUP50:IMPORTIN-ALPHA COMPLEX
Template:ABSTRACT PUBMED 16222336
About this Structure
2c1m is a 2 chain structure with sequence from Mus musculus. Full crystallographic information is available from OCA.
See Also
IMPORTIN ALPHA STRUCTURE
Importin α is a soluble adaptor protein also known as karyopherin α. It has as a function to connect importin β and a protein which have a cNLS (classical Nuclear Localization Signal) in order to import this protein in the nucleus. A NLS is a basic residue-rich sequence with the following consensus sequence :
- Two adjacent basic amino acids (Arg or Lys).
- A spacer region of any 10 residues.
- At least three basic residues (Arg or Lys) in the five positions after the spacer region.
Importin α is composed of different domains:
- A flexible, hydrophilic 10kDa N-terminal Importin β binding domain (IBB domain). The IBB domain is an L-shapped molecule with an N-terminal extended moiety and a C-terminal helix running in mutually perpendicular directions. Because this domain is highly positively charged, it can binds to the inner surface of importin-β that contains many acidic residues. It has been shown that importin α contains a determinant which is sufficint for binding to importin β. The consensus sequence of this determinant is KFRLLSKE. The serine contained in this sequence is present in all importin α. However, the upstream region is sufficient for binding importin β too. Nowadays, we think that this region contribute to the strength of the bond. This could explain the fact that the binding between importin α and β is stronger when α contains these two determinants.
- A 50kDa C-terminal NLS-binding site composed of 10 tandem armadillo (Arm) repeats. These arm repeat domains have an elongated superhelical structure and each of them contains 3 α-helices (H1, H2, H3). H3 helices define the inner concave surface of the protein and the NLS-binding site.
- Surprisingly, it also contains an NLS. Thus, it is belongs to the group of proteins containing both a ligand (NLS) and a cognate receptor (NLS-binding site). That’s why it could have a possibility of autologous ligand-receptor interactions. Nevertheless, it has been shown that NLS of importin α overlaps with the IBB. Thereby, binding of importin β to importin α covers the NLS of importin α preventing autologous ligand receptor interactions.
Reference
- Matsuura Y, Stewart M. Nup50/Npap60 function in nuclear protein import complex disassembly and importin recycling. EMBO J. 2005 Nov 2;24(21):3681-9. Epub 2005 Oct 13. PMID:16222336
