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1ee4

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Revision as of 09:36, 21 July 2021

CRYSTAL STRUCTURE OF YEAST KARYOPHERIN (IMPORTIN) ALPHA IN A COMPLEX WITH A C-MYC NLS PEPTIDE

Structural highlights

1ee4 is a 6 chain structure with sequence from Atcc 18824 and Human. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Related:	1bk6, 1ee5
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Disease

[MYC_HUMAN] Note=Overexpression of MYC is implicated in the etiology of a variety of hematopoietic tumors. Note=A chromosomal aberration involving MYC may be a cause of a form of B-cell chronic lymphocytic leukemia. Translocation t(8;12)(q24;q22) with BTG1. Defects in MYC are a cause of Burkitt lymphoma (BL) [MIM:113970]. A form of undifferentiated malignant lymphoma commonly manifested as a large osteolytic lesion in the jaw or as an abdominal mass. Note=Chromosomal aberrations involving MYC are usually found in Burkitt lymphoma. Translocations t(8;14), t(8;22) or t(2;8) which juxtapose MYC to one of the heavy or light chain immunoglobulin gene loci.

Function

[IMA1_YEAST] Binds specifically and directly to substrates containing either a simple or bipartite NLS motif. Promotes docking of import substrates to the nuclear envelope. Seems to act as a cytosolic receptor for both simple and bipartite NLS motifs (By similarity).^[1] ^[2] ^[3] [MYC_HUMAN] Participates in the regulation of gene transcription. Binds DNA in a non-specific manner, yet also specifically recognizes the core sequence 5'-CAC[GA]TG-3'. Seems to activate the transcription of growth-related genes.

Evolutionary Conservation

Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.

Publication Abstract from PubMed

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. 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. 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.

Crystallographic analysis of the specific yet versatile recognition of distinct nuclear localization signals by karyopherin alpha.,Conti E, Kuriyan J Structure. 2000 Mar 15;8(3):329-38. PMID:10745017^[4]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Kussel P, Frasch M. Yeast Srp1, a nuclear protein related to Drosophila and mouse pendulin, is required for normal migration, division, and integrity of nuclei during mitosis. Mol Gen Genet. 1995 Aug 21;248(3):351-63. PMID:7565597
↑ Tabb MM, Tongaonkar P, Vu L, Nomura M. Evidence for separable functions of Srp1p, the yeast homolog of importin alpha (Karyopherin alpha): role for Srp1p and Sts1p in protein degradation. Mol Cell Biol. 2000 Aug;20(16):6062-73. PMID:10913188
↑ Chen L, Romero L, Chuang SM, Tournier V, Joshi KK, Lee JA, Kovvali G, Madura K. Sts1 plays a key role in targeting proteasomes to the nucleus. J Biol Chem. 2011 Jan 28;286(4):3104-18. doi: 10.1074/jbc.M110.135863. Epub 2010 , Nov 12. PMID:21075847 doi:10.1074/jbc.M110.135863
↑ Conti E, Kuriyan J. Crystallographic analysis of the specific yet versatile recognition of distinct nuclear localization signals by karyopherin alpha. Structure. 2000 Mar 15;8(3):329-38. PMID:10745017

1 Structural highlights
2 Disease
3 Function
4 Evolutionary Conservation
5 Publication Abstract from PubMed
6 See Also
7 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/1ee4"

@@ Line 3: / Line 3: @@
 <StructureSection load='1ee4' size='340' side='right'caption='[[1ee4]], [[Resolution|resolution]] 2.10&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[1ee4]] is a 6 chain structure with sequence from [http://en.wikipedia.org/wiki/Atcc_18824 Atcc 18824] and [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1EE4 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1EE4 FirstGlance]. <br>
+<table><tr><td colspan='2'>[[1ee4]] is a 6 chain structure with sequence from [https://en.wikipedia.org/wiki/Atcc_18824 Atcc 18824] and [https://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1EE4 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1EE4 FirstGlance]. <br>
-</td></tr><tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[1bk6|1bk6]], [[1ee5|1ee5]]</td></tr>
+</td></tr><tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[1bk6|1bk6]], [[1ee5|1ee5]]</div></td></tr>
-<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1ee4 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1ee4 OCA], [http://pdbe.org/1ee4 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=1ee4 RCSB], [http://www.ebi.ac.uk/pdbsum/1ee4 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=1ee4 ProSAT]</span></td></tr>
+<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=1ee4 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1ee4 OCA], [https://pdbe.org/1ee4 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1ee4 RCSB], [https://www.ebi.ac.uk/pdbsum/1ee4 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1ee4 ProSAT]</span></td></tr>
 </table>
 == Disease ==
-[[http://www.uniprot.org/uniprot/MYC_HUMAN MYC_HUMAN]] Note=Overexpression of MYC is implicated in the etiology of a variety of hematopoietic tumors.  Note=A chromosomal aberration involving MYC may be a cause of a form of B-cell chronic lymphocytic leukemia. Translocation t(8;12)(q24;q22) with BTG1.  Defects in MYC are a cause of Burkitt lymphoma (BL) [MIM:[http://omim.org/entry/113970 113970]]. A form of undifferentiated malignant lymphoma commonly manifested as a large osteolytic lesion in the jaw or as an abdominal mass. Note=Chromosomal aberrations involving MYC are usually found in Burkitt lymphoma. Translocations t(8;14), t(8;22) or t(2;8) which juxtapose MYC to one of the heavy or light chain immunoglobulin gene loci.
+[[https://www.uniprot.org/uniprot/MYC_HUMAN MYC_HUMAN]] Note=Overexpression of MYC is implicated in the etiology of a variety of hematopoietic tumors.  Note=A chromosomal aberration involving MYC may be a cause of a form of B-cell chronic lymphocytic leukemia. Translocation t(8;12)(q24;q22) with BTG1.  Defects in MYC are a cause of Burkitt lymphoma (BL) [MIM:[https://omim.org/entry/113970 113970]]. A form of undifferentiated malignant lymphoma commonly manifested as a large osteolytic lesion in the jaw or as an abdominal mass. Note=Chromosomal aberrations involving MYC are usually found in Burkitt lymphoma. Translocations t(8;14), t(8;22) or t(2;8) which juxtapose MYC to one of the heavy or light chain immunoglobulin gene loci.
 == Function ==
-[[http://www.uniprot.org/uniprot/IMA1_YEAST IMA1_YEAST]] Binds specifically and directly to substrates containing either a simple or bipartite NLS motif. Promotes docking of import substrates to the nuclear envelope. Seems to act as a cytosolic receptor for both simple and bipartite NLS motifs (By similarity).<ref>PMID:7565597</ref> <ref>PMID:10913188</ref> <ref>PMID:21075847</ref>  [[http://www.uniprot.org/uniprot/MYC_HUMAN MYC_HUMAN]] Participates in the regulation of gene transcription. Binds DNA in a non-specific manner, yet also specifically recognizes the core sequence 5'-CAC[GA]TG-3'. Seems to activate the transcription of growth-related genes.
+[[https://www.uniprot.org/uniprot/IMA1_YEAST IMA1_YEAST]] Binds specifically and directly to substrates containing either a simple or bipartite NLS motif. Promotes docking of import substrates to the nuclear envelope. Seems to act as a cytosolic receptor for both simple and bipartite NLS motifs (By similarity).<ref>PMID:7565597</ref> <ref>PMID:10913188</ref> <ref>PMID:21075847</ref>  [[https://www.uniprot.org/uniprot/MYC_HUMAN MYC_HUMAN]] Participates in the regulation of gene transcription. Binds DNA in a non-specific manner, yet also specifically recognizes the core sequence 5'-CAC[GA]TG-3'. Seems to activate the transcription of growth-related genes.
 == Evolutionary Conservation ==
 [[Image:Consurf_key_small.gif|200px|right]]

1ee4

From Proteopedia

Revision as of 09:36, 21 July 2021

CRYSTAL STRUCTURE OF YEAST KARYOPHERIN (IMPORTIN) ALPHA IN A COMPLEX WITH A C-MYC NLS PEPTIDE

Structural highlights

Disease

Function

Evolutionary Conservation

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

Views

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