2ast

From Proteopedia

(Difference between revisions)
Jump to: navigation, search
Line 1: Line 1:
-
{{STRUCTURE_2ast| PDB=2ast | SCENE= }}
+
==Crystal structure of Skp1-Skp2-Cks1 in complex with a p27 peptide==
-
===Crystal structure of Skp1-Skp2-Cks1 in complex with a p27 peptide===
+
<StructureSection load='2ast' size='340' side='right' caption='[[2ast]], [[Resolution|resolution]] 2.30&Aring;' scene=''>
-
{{ABSTRACT_PUBMED_16209941}}
+
== Structural highlights ==
 +
<table><tr><td colspan='2'>[[2ast]] is a 4 chain structure with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2AST OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2AST FirstGlance]. <br>
 +
</td></tr><tr><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=BEN:BENZAMIDINE'>BEN</scene><br>
 +
<tr><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=TPO:PHOSPHOTHREONINE'>TPO</scene></td></tr>
 +
<tr><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[2ass|2ass]], [[1fqv|1fqv]]</td></tr>
 +
<tr><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">SKP1A, EMC19, OCP2, SKP1, TCEB1L ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens]), SKP2, FBXL1 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens]), CKS1, CKS1B ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens])</td></tr>
 +
<tr><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2ast FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2ast OCA], [http://www.rcsb.org/pdb/explore.do?structureId=2ast RCSB], [http://www.ebi.ac.uk/pdbsum/2ast PDBsum]</span></td></tr>
 +
<table>
 +
== Disease ==
 +
[[http://www.uniprot.org/uniprot/CDN1B_HUMAN CDN1B_HUMAN]] Defects in CDKN1B are the cause of multiple endocrine neoplasia type 4 (MEN4) [MIM:[http://omim.org/entry/610755 610755]]. Multiple endocrine neoplasia (MEN) syndromes are inherited cancer syndromes of the thyroid. MEN4 is a MEN-like syndrome with a phenotypic overlap of both MEN1 and MEN2.<ref>PMID:17030811</ref>
 +
== Function ==
 +
[[http://www.uniprot.org/uniprot/CDN1B_HUMAN CDN1B_HUMAN]] Important regulator of cell cycle progression. Involved in G1 arrest. Potent inhibitor of cyclin E- and cyclin A-CDK2 complexes. Forms a complex with cyclin type D-CDK4 complexes and is involved in the assembly, stability, and modulation of CCND1-CDK4 complex activation. Acts either as an inhibitor or an activator of cyclin type D-CDK4 complexes depending on its phosphorylation state and/or stoichometry.<ref>PMID:10831586</ref> <ref>PMID:12244301</ref> <ref>PMID:16782892</ref> <ref>PMID:19075005</ref> <ref>PMID:17254966</ref> [[http://www.uniprot.org/uniprot/SKP1_HUMAN SKP1_HUMAN]] Essential component of the SCF (SKP1-CUL1-F-box protein) ubiquitin ligase complex, which mediates the ubiquitination of proteins involved in cell cycle progression, signal transduction and transcription. In the SCF complex, serves as an adapter that links the F-box protein to CUL1. SCF(BTRC) mediates the ubiquitination of NFKBIA at 'Lys-21' and 'Lys-22'; the degradation frees the associated NFKB1-RELA dimer to translocate into the nucleus and to activate transcription. SCF(Cyclin F) directs ubiquitination of CP110.<ref>PMID:16209941</ref> <ref>PMID:20181953</ref> [[http://www.uniprot.org/uniprot/CKS1_HUMAN CKS1_HUMAN]] Binds to the catalytic subunit of the cyclin dependent kinases and is essential for their biological function. [[http://www.uniprot.org/uniprot/SKP2_HUMAN SKP2_HUMAN]] Substrate recognition component of a SCF (SKP1-CUL1-F-box protein) E3 ubiquitin-protein ligase complex which mediates the ubiquitination and subsequent proteasomal degradation of target proteins involved in cell cycle progression, signal transduction and transcription. Specifically recognizes phosphorylated CDKN1B/p27kip and is involved in regulation of G1/S transition. Degradation of CDKN1B/p27kip also requires CKS1. Recognizes target proteins ORC1, CDT1, RBL2, MLL, CDK9, RAG2, FOXO1, UBP43, and probably MYC, TOB1 and TAL1. Degradation of TAL1 also requires STUB1. Recognizes CDKN1A in association with CCNE1 or CCNE2 and CDK2. Promotes ubiquitination and destruction of CDH1 in a CK1-Dependent Manner, thereby regulating cell migration.<ref>PMID:12435635</ref> <ref>PMID:11931757</ref> <ref>PMID:12840033</ref> <ref>PMID:12769844</ref> <ref>PMID:15342634</ref> <ref>PMID:16262255</ref> <ref>PMID:15949444</ref> <ref>PMID:16103164</ref> <ref>PMID:15668399</ref> <ref>PMID:16951159</ref> <ref>PMID:16581786</ref> <ref>PMID:17908926</ref> <ref>PMID:17962192</ref> <ref>PMID:22770219</ref>
 +
== Evolutionary Conservation ==
 +
[[Image:Consurf_key_small.gif|200px|right]]
 +
Check<jmol>
 +
<jmolCheckbox>
 +
<scriptWhenChecked>select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/as/2ast_consurf.spt"</scriptWhenChecked>
 +
<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
 +
<text>to colour the structure by Evolutionary Conservation</text>
 +
</jmolCheckbox>
 +
</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/chain_selection.php?pdb_ID=2ata ConSurf].
 +
<div style="clear:both"></div>
 +
<div style="background-color:#fffaf0;">
 +
== Publication Abstract from PubMed ==
 +
The ubiquitin-mediated proteolysis of the Cdk2 inhibitor p27(Kip1) plays a central role in cell cycle progression, and enhanced degradation of p27(Kip1) is associated with many common cancers. Proteolysis of p27(Kip1) is triggered by Thr187 phosphorylation, which leads to the binding of the SCF(Skp2) (Skp1-Cul1-Rbx1-Skp2) ubiquitin ligase complex. Unlike other known SCF substrates, p27(Kip1) ubiquitination also requires the accessory protein Cks1. The crystal structure of the Skp1-Skp2-Cks1 complex bound to a p27(Kip1) phosphopeptide shows that Cks1 binds to the leucine-rich repeat (LRR) domain and C-terminal tail of Skp2, whereas p27(Kip1) binds to both Cks1 and Skp2. The phosphorylated Thr187 side chain of p27(Kip1) is recognized by a Cks1 phosphate binding site, whereas the side chain of an invariant Glu185 inserts into the interface between Skp2 and Cks1, interacting with both. The structure and biochemical data support the proposed model that Cdk2-cyclin A contributes to the recruitment of p27(Kip1) to the SCF(Skp2)-Cks1 complex.
-
==Disease==
+
Structural basis of the Cks1-dependent recognition of p27(Kip1) by the SCF(Skp2) ubiquitin ligase.,Hao B, Zheng N, Schulman BA, Wu G, Miller JJ, Pagano M, Pavletich NP Mol Cell. 2005 Oct 7;20(1):9-19. PMID:16209941<ref>PMID:16209941</ref>
-
[[http://www.uniprot.org/uniprot/CDN1B_HUMAN CDN1B_HUMAN]] Defects in CDKN1B are the cause of multiple endocrine neoplasia type 4 (MEN4) [MIM:[http://omim.org/entry/610755 610755]]. Multiple endocrine neoplasia (MEN) syndromes are inherited cancer syndromes of the thyroid. MEN4 is a MEN-like syndrome with a phenotypic overlap of both MEN1 and MEN2.<ref>PMID:17030811</ref>
+
-
==Function==
+
From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
-
[[http://www.uniprot.org/uniprot/CDN1B_HUMAN CDN1B_HUMAN]] Important regulator of cell cycle progression. Involved in G1 arrest. Potent inhibitor of cyclin E- and cyclin A-CDK2 complexes. Forms a complex with cyclin type D-CDK4 complexes and is involved in the assembly, stability, and modulation of CCND1-CDK4 complex activation. Acts either as an inhibitor or an activator of cyclin type D-CDK4 complexes depending on its phosphorylation state and/or stoichometry.<ref>PMID:10831586</ref><ref>PMID:12244301</ref><ref>PMID:16782892</ref><ref>PMID:19075005</ref><ref>PMID:17254966</ref> [[http://www.uniprot.org/uniprot/SKP1_HUMAN SKP1_HUMAN]] Essential component of the SCF (SKP1-CUL1-F-box protein) ubiquitin ligase complex, which mediates the ubiquitination of proteins involved in cell cycle progression, signal transduction and transcription. In the SCF complex, serves as an adapter that links the F-box protein to CUL1. SCF(BTRC) mediates the ubiquitination of NFKBIA at 'Lys-21' and 'Lys-22'; the degradation frees the associated NFKB1-RELA dimer to translocate into the nucleus and to activate transcription. SCF(Cyclin F) directs ubiquitination of CP110.<ref>PMID:16209941</ref><ref>PMID:20181953</ref> [[http://www.uniprot.org/uniprot/CKS1_HUMAN CKS1_HUMAN]] Binds to the catalytic subunit of the cyclin dependent kinases and is essential for their biological function. [[http://www.uniprot.org/uniprot/SKP2_HUMAN SKP2_HUMAN]] Substrate recognition component of a SCF (SKP1-CUL1-F-box protein) E3 ubiquitin-protein ligase complex which mediates the ubiquitination and subsequent proteasomal degradation of target proteins involved in cell cycle progression, signal transduction and transcription. Specifically recognizes phosphorylated CDKN1B/p27kip and is involved in regulation of G1/S transition. Degradation of CDKN1B/p27kip also requires CKS1. Recognizes target proteins ORC1, CDT1, RBL2, MLL, CDK9, RAG2, FOXO1, UBP43, and probably MYC, TOB1 and TAL1. Degradation of TAL1 also requires STUB1. Recognizes CDKN1A in association with CCNE1 or CCNE2 and CDK2. Promotes ubiquitination and destruction of CDH1 in a CK1-Dependent Manner, thereby regulating cell migration.<ref>PMID:12435635</ref><ref>PMID:11931757</ref><ref>PMID:12840033</ref><ref>PMID:12769844</ref><ref>PMID:15342634</ref><ref>PMID:16262255</ref><ref>PMID:15949444</ref><ref>PMID:16103164</ref><ref>PMID:15668399</ref><ref>PMID:16951159</ref><ref>PMID:16581786</ref><ref>PMID:17908926</ref><ref>PMID:17962192</ref><ref>PMID:22770219</ref>
+
</div>
-
 
+
== References ==
-
==About this Structure==
+
<references/>
-
[[2ast]] is a 4 chain structure with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2AST OCA].
+
__TOC__
-
 
+
</StructureSection>
-
==Reference==
+
-
<ref group="xtra">PMID:016209941</ref><references group="xtra"/><references/>
+
[[Category: Homo sapiens]]
[[Category: Homo sapiens]]
[[Category: Hao, B.]]
[[Category: Hao, B.]]

Revision as of 00:14, 30 September 2014

Crystal structure of Skp1-Skp2-Cks1 in complex with a p27 peptide

2ast, resolution 2.30Å

Drag the structure with the mouse to rotate

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/2ast"
Views
Personal tools
Navigation
Toolbox