Database Accession: DI1110008
Name: Karyopheryn (importin) alpha in complex with nucleoplasmin NLS peptide
PDB ID: 1ee5
Experimental method: X-ray (2.40 Å)
Source organism: Xenopus laevis / Saccharomyces cerevisiae
Proof of disorder:
Primary publication of the structure:
Conti E, Kuriyan J
Crystallographic analysis of the specific yet versatile recognition of distinct nuclear localization signals by karyopherin alpha.
(2000) Structure 8: 329-38
CONCLUSIONS: Monopartite and bipartite NLSs bind to a different number of amino acid binding pockets and make different interactions within them. The relatively hydrophobic monopartite c-myc NLS binds extensively at a few binding pockets in a similar manner to that of the SV40 T antigen NLS. In contrast, the bipartite nucleoplasmin NLS engages the whole array of pockets with individually more limited but overall more abundant interactions, which include the NLS two basic clusters and the backbone of its non-conserved linker region. Versatility in the specific recognition of NLSs relies on the modular.
RESULTS: We report the crystal structures of two peptide complexes of yeast karyopherin alpha (Kapalpha): one with a human c-myc NLS peptide, determined at 2.1 A resolution, and one with a Xenopus nucleoplasmin NLS peptide, determined at 2.4 A resolution. Analysis of these structures reveals the determinants of specificity for the binding of a relatively hydrophobic monopartite NLS and of a bipartite NLS peptide. The peptides bind Kapalpha in its extended surface groove, which presents a modular array of tandem binding pockets for amino acid residues.
BACKGROUND: Karyopherin alpha (importin alpha) is an adaptor molecule that recognizes proteins containing nuclear localization signals (NLSs). The prototypical NLS that is able to bind to karyopherin alpha is that of the SV40 T antigen, and consists of a short positively charged sequence motif. Distinct classes of NLSs (monopartite and bipartite) have been identified that are only partly conserved with respect to one another but are nevertheless recognized by the same receptor.
Molecular function: not assigned
Biological process: not assigned
Entry contents: 2 distinct polypeptide molecules
Chains: B, A
Notes: No modifications of the original PDB file.
Source organism: Xenopus laevis
Length: 19 residues
Sequence:Sequence according to PDB SEQRESAVKRPAATKKAGQAKKKKL
UniProtKB AC: P05221 (positions: 153-171)Coverage: 9.5%
UniRef90 AC: UniRef90_P05221 (positions: 153-171)
Name: Importin subunit alpha
Source organism: Saccharomyces cerevisiae
Length: 421 residues
Sequence:Sequence according to PDB SEQRESPQMTQQLNSDDMQEQLSATVKFRQILSREHRPPIDVVIQAGVVPRLVEFMRENQPEMLQLEAAWALTNIASGTSAQTKVVVDADAVPLFIQLLYTGSVEVKEQAIWALGNVAGDSTDYRDYVLQCNAMEPILGLFNSNKPSLIRTATWTLSNLCRGKKPQPDWSVVSQALPTLAKLIYSMDTETLVDACWAISYLSDGPQEAIQAVIDVRIPKRLVELLSHESTLVQTPALRAVGNIVTGNDLQTQVVINAGVLPALRLLLSSPKENIKKEACWTISNITAGNTEQIQAVIDANLIPPLVKLLEVAEYKTKKEACWAISNASSGGLQRPDIIRYLVSQGCIKPLCDLLEIADNRIIEVTLDALENILKMGEADKEARGLNINENADFIEKAGGMEKIFNCQQNENDKIYEKAYKIIETYFG
UniProtKB AC: Q02821 (positions: 90-510)Coverage: 77.7%
UniRef90 AC: UniRef90_Q02821 (positions: 90-510)
The 120-200 region described in DisProt entry DP00217 cover 100% of the sequence present in the structure. The protein region involved in the interaction contains a known functional linear motif (TRG_NLS_Bipartite_1).
The armadillo repeat domain involved in the interaction is known to adopt a stable structure in isolation (see Pfam domain PF00514). A solved monomeric structure of the domain from a homologous protein is represented by PDB ID 1ial.
No related structure was found in the Protein Data Bank.