Database Accession: DI1010066
Name: Yeast karyopherin (importin) alpha in complex with a c-Myc NLS peptide
PDB ID: 1ee4
Experimental method: X-ray (2.10 Å)
Source organism: Homo sapiens / 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.
transport The directed movement of substances (such as macromolecules, small molecules, ions) or cellular components (such as complexes and organelles) into, out of or within a cell, or between cells, or within a multicellular organism by means of some agent such as a transporter, pore or motor protein.
protein complex A stable macromolecular complex composed (only) of two or more polypeptide subunits along with any covalently attached molecules (such as lipid anchors or oligosaccharide) or non-protein prosthetic groups (such as nucleotides or metal ions). Prosthetic group in this context refers to a tightly bound cofactor. The component polypeptide subunits may be identical.
Entry contents: 2 distinct polypeptide molecules
Chains: C, A
Notes: Chains D, B, E and F were removed as chains C and A highlight the biologically relevant interaction.
Name: Myc proto-oncogene protein
Source organism: Homo sapiens
Length: 9 residues
Sequence:Sequence according to PDB SEQRESMSTVHEILSKLSLE
UniProtKB AC: P01106 (positions: 320-328)Coverage: 2.1%
UniRef90 AC: UniRef90_P01106 (positions: 320-328)
Name: Importin subunit alpha
Source organism: Saccharomyces cerevisiae
Length: 423 residues
Sequence:Sequence according to PDB SEQRESQELPQMTQQLNSDDMQEQLSATVKFRQILSREHRPPIDVVIQAGVVPRLVEFMRENQPEMLQLEAAWALTNIASGTSAQTKVVVDADAVPLFIQLLYTGSVEVKEQAIWALGNVAGDSTDYRDYVLQCNAMEPILGLFNSNKPSLIRTATWTLSNLCRGKKPQPDWSVVSQALPTLAKLIYSMDTETLVDACWAISYLSDGPQEAIQAVIDVRIPKRLVELLSHESTLVQTPALRAVGNIVTGNDLQTQVVINAGVLPALRLLLSSPKENIKKEACWTISNITAGNTEQIQAVIDANLIPPLVKLLEVAEDKTKKEACWAISNASSGGLQRPDIIRYLVSQGCIKPLCDLLEIADNRIIEVTLDALENILKMGEADKEARGLNINENADFIEKAGGMEKIFNCQQNENDKIYEKAYKIIETYF
UniProtKB AC: Q02821 (positions: 87-509)Coverage: 78%
UniRef90 AC: UniRef90_Q02821 (positions: 87-509)
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 is represented by PDB ID 1bk5.
No related structure was found in the Protein Data Bank.
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