General Information

Database Accession: DI1010066

Name: Yeast karyopherin (importin) alpha in complex with a c-Myc NLS peptide

PDB ID: 1ee4 PDB

Experimental method: X-ray (2.10 Å)

Source organism: Homo sapiens / Saccharomyces cerevisiae

Proof of disorder: Inferred from motif

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

PMID: 10745017 PubMed

Abstract:

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.

Function and Biology Annotations from the GeneOntology database. Only terms that fit at least two of the interacting proteins are shown.

Molecular function:

protein binding Interacting selectively and non-covalently with any protein or protein complex (a complex of two or more proteins that may include other nonprotein molecules). GeneOntology

Biological process:

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. GeneOntology

Cellular component:

nucleoplasm That part of the nuclear content other than the chromosomes or the nucleolus. GeneOntology

cytosol The part of the cytoplasm that does not contain organelles but which does contain other particulate matter, such as protein complexes. GeneOntology

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. GeneOntology

Structure Summary Structural annotations of the participating protein chains.

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.

Chain C

Name: Myc proto-oncogene protein Disordered Inferred from motif

Source organism: Homo sapiens

Length: 9 residues

Sequence:Sequence according to PDB SEQRESMSTVHEILSKLSLE

UniProtKB AC: P01106 (positions: 320-328) UniProt Coverage: 2.1%

UniRef90 AC: UniRef90_P01106 (positions: 320-328) UniRef90

Chain A

Name: Importin subunit alpha Ordered

Source organism: Saccharomyces cerevisiae

Length: 423 residues

Sequence:Sequence according to PDB SEQRESQELPQMTQQLNSDDMQEQLSATVKFRQILSREHRPPIDVVIQAGVVPRLVEFMRENQPEMLQLEAAWALTNIASGTSAQTKVVVDADAVPLFIQLLYTGSVEVKEQAIWALGNVAGDSTDYRDYVLQCNAMEPILGLFNSNKPSLIRTATWTLSNLCRGKKPQPDWSVVSQALPTLAKLIYSMDTETLVDACWAISYLSDGPQEAIQAVIDVRIPKRLVELLSHESTLVQTPALRAVGNIVTGNDLQTQVVINAGVLPALRLLLSSPKENIKKEACWTISNITAGNTEQIQAVIDANLIPPLVKLLEVAEDKTKKEACWAISNASSGGLQRPDIIRYLVSQGCIKPLCDLLEIADNRIIEVTLDALENILKMGEADKEARGLNINENADFIEKAGGMEKIFNCQQNENDKIYEKAYKIIETYF

UniProtKB AC: Q02821 (positions: 87-509) UniProt Coverage: 78%

UniRef90 AC: UniRef90_Q02821 (positions: 87-509) UniRef90

Evidence Evidence demonstrating that the participating proteins are unstructured prior to the interaction and their folding is coupled to binding.

Chain C: Disordered Inferred from motif

The protein region involved in the interaction contains 2 known functional linear motifs (TRG_NLS_MonoExtC_3, TRG_NLS_MonoExtN_4).

Chain A: Ordered

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.

Related Structure(s) Structures from the PDB that contain the same number of proteins, and the proteins from the two structures show a sufficient degree of pairwise similarity, i.e. they belong to the same UniRef90 cluster (the full proteins exhibit at least 90% sequence identity) and convey roughly the same region to their respective interactions (the two regions from the two proteins share a minimum of 70% overlap).

No related structure was found in the Protein Data Bank.

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