DI1010066
Yeast karyopherin (importin) alpha in complex with a c-Myc NLS peptide
1ee4
X-ray
2.10
Homo sapiens / Saccharomyces cerevisiae
Inferred from motif
10745017
Conti E, Kuriyan J
Crystallographic analysis of the specific yet versatile recognition of distinct nuclear localization signals by karyopherin alpha.
Structure
2000
3
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.
GO:0005515
protein binding
GO:0006810
transport
GO:0005654
nucleoplasm
GO:0005829
cytosol
GO:0043234
protein complex
Chains D, B, E and F were removed as chains C and A highlight the biologically relevant interaction.
2
Armadillo repeat
C
Myc proto-oncogene protein
Disordered
Homo sapiens
MSTVHEILSKLSLE
9
P01106
320
328
2.1%
UniRef90_P01106
320
328
pfam
PF01056.15
Myc_N
1
345
A
Importin subunit alpha
Ordered
Saccharomyces cerevisiae
QELPQMTQQLNSDDMQEQLSATVKFRQILSREHRPPIDVVIQAGVVPRLVEFMRENQPEMLQLEAAWALTNIASGTSAQTKVVVDADAVPLFIQLLYTGSVEVKEQAIWALGNVAGDSTDYRDYVLQCNAMEPILGLFNSNKPSLIRTATWTLSNLCRGKKPQPDWSVVSQALPTLAKLIYSMDTETLVDACWAISYLSDGPQEAIQAVIDVRIPKRLVELLSHESTLVQTPALRAVGNIVTGNDLQTQVVINAGVLPALRLLLSSPKENIKKEACWTISNITAGNTEQIQAVIDANLIPPLVKLLEVAEDKTKKEACWAISNASSGGLQRPDIIRYLVSQGCIKPLCDLLEIADNRIIEVTLDALENILKMGEADKEARGLNINENADFIEKAGGMEKIFNCQQNENDKIYEKAYKIIETYF
423
Q02821
87
509
78%
UniRef90_Q02821
87
509
secondary structure
helix
89
96
secondary structure
helix
101
115
secondary structure
helix
123
128
secondary structure
helix
132
137
secondary structure
helix
145
158
secondary structure
helix
163
171
secondary structure
helix
174
184
secondary structure
helix
187
201
secondary structure
helix
205
213
secondary structure
helix
217
223
secondary structure
helix
229
243
secondary structure
helix
252
265
secondary structure
helix
271
284
secondary structure
helix
289
297
secondary structure
helix
300
307
secondary structure
helix
313
326
secondary structure
helix
331
339
secondary structure
helix
342
349
secondary structure
helix
355
368
secondary structure
helix
373
381
secondary structure
helix
385
394
secondary structure
helix
397
415
secondary structure
helix
418
426
secondary structure
helix
430
438
secondary structure
helix
442
465
secondary structure
helix
472
479
secondary structure
helix
482
489
secondary structure
helix
495
508
pfam
PF01749.17
IBB
17
109
pfam
PF00514.20
Arm
119
160
pfam
PF00514.20
Arm
162
202
pfam
PF00514.20
Arm
204
244
pfam
PF00514.20
Arm
246
286
pfam
PF00514.20
Arm
288
328
pfam
PF00514.20
Arm
330
370
pfam
PF00514.20
Arm
372
412
pfam
PF00514.20
Arm
417
457
pfam
PF16186.2
Arm_3
471
523
C
The protein region involved in the interaction contains 2 known functional linear motifs (TRG_NLS_MonoExtC_3, TRG_NLS_MonoExtN_4).
A
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.