3ns8: Difference between revisions

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[[~~Image~~:~~3ns8~~.~~png~~|~~left~~|~~200px~~]]

==Crystal structure of an open conformation of Lys48-linked diubiquitin at pH 7.5==

== Structural highlights ==

<table><tr><td colspan='2'>[[3ns8]] is a 2 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=3NS8 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3NS8 FirstGlance]. <br>

</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=EPE:4-(2-HYDROXYETHYL)-1-PIPERAZINE+ETHANESULFONIC+ACID'>EPE</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene></td></tr>

<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">RPS27A ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens])</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=3ns8 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3ns8 OCA], [http://www.rcsb.org/pdb/explore.do?structureId=3ns8 RCSB], [http://www.ebi.ac.uk/pdbsum/3ns8 PDBsum]</span></td></tr>

</table>

== Publication Abstract from PubMed ==

Ubiquitin (Ub) is a small protein highly conserved among eukaryotes and involved in practically all aspects of eukaryotic cell biology. Polymeric chains assembled from covalently-linked Ub monomers function as molecular signals in the regulation of a host of cellular processes. Our previous studies have shown that the predominant state of Lys48-linked di- and tetra-Ub chains at near-physiological conditions is a closed conformation, in which the Ub-Ub interface is formed by the hydrophobic surface residues of the adjacent Ub units. Because these very residues are involved in (poly)Ub interactions with the majority of Ub-binding proteins, their sequestration at the Ub-Ub interface renders the closed conformation of polyUb binding incompetent. Thus the existence of open conformation(s) and the interdomain motions opening and closing the Ub-Ub interface is critical for the recognition of Lys48-linked polyUb by its receptors. Knowledge of the conformational properties of a polyUb signal is essential for our understanding of its specific recognition by various Ub-receptors. Despite their functional importance, open states of Lys48-linked chains are poorly characterized. Here we report a crystal structure of the open state of Lys48-linked di-Ub. Moreover, using NMR, we examined interactions of the open state of this chain (at pH4.5) with a Lys48-linkage-selective receptor, the UBA2 domain of a shuttle protein hHR23a. Our results show that di-Ub binds UBA2 in the same mode and with comparable affinity as the closed state. Our data suggest a mechanism for polyUb signal recognition, whereby Ub-binding proteins select specific conformations out of the available ensemble of polyUb chain conformations. This article is part of a Special Issue entitled: Ubiquitin Drug Discovery and Diagnostics.

~~{{STRUCTURE_3ns8| PDB=3ns8 | SCENE= }}~~

Structural and biochemical studies of the open state of Lys48-linked diubiquitin.,Lai MY, Zhang D, Laronde-Leblanc N, Fushman D Biochim Biophys Acta. 2012 Nov;1823(11):2046-56. doi:, 10.1016/j.bbamcr.2012.04.003. Epub 2012 Apr 16. PMID:22542781<ref>PMID:22542781</ref>

~~===Crystal structure~~ of ~~an open conformation~~ of ~~Lys48-linked diubiquitin at pH 7~~.~~5===~~

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

</div>

~~{{ABSTRACT_PUBMED_22542781}}~~

~~==About this Structure==~~

~~[[3ns8]] is a 2 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=3NS8 OCA].~~

==See Also==

*[[Ubiquitin|Ubiquitin]]

== References ==

__TOC__

</StructureSection>

[[Category: Homo sapiens]]

[[Category: Fushman, D.]]

[[Category: Fushman, D]]

[[Category: LaRonde-LeBlanc, N.]]

[[Category: LaRonde-LeBlanc, N]]

[[Category: Zhang, D.]]

[[Category: Zhang, D]]

[[Category: Diubiquitin]]

[[Category: Isopeptide bond]]

[[Category: Signaling protein]]

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@@ Line 1: / Line 1: @@
-[[Image:3ns8.png|left|200px]]
+==Crystal structure of an open conformation of Lys48-linked diubiquitin at pH 7.5==
+<StructureSection load='3ns8' size='340' side='right' caption='[[3ns8]], [[Resolution|resolution]] 1.71&Aring;' scene=''>
+== Structural highlights ==
+<table><tr><td colspan='2'>[[3ns8]] is a 2 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=3NS8 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3NS8 FirstGlance]. <br>
+</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=EPE:4-(2-HYDROXYETHYL)-1-PIPERAZINE+ETHANESULFONIC+ACID'>EPE</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene></td></tr>
+<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">RPS27A ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens])</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=3ns8 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3ns8 OCA], [http://www.rcsb.org/pdb/explore.do?structureId=3ns8 RCSB], [http://www.ebi.ac.uk/pdbsum/3ns8 PDBsum]</span></td></tr>
+</table>
+<div style="background-color:#fffaf0;">
+== Publication Abstract from PubMed ==
+Ubiquitin (Ub) is a small protein highly conserved among eukaryotes and involved in practically all aspects of eukaryotic cell biology. Polymeric chains assembled from covalently-linked Ub monomers function as molecular signals in the regulation of a host of cellular processes. Our previous studies have shown that the predominant state of Lys48-linked di- and tetra-Ub chains at near-physiological conditions is a closed conformation, in which the Ub-Ub interface is formed by the hydrophobic surface residues of the adjacent Ub units. Because these very residues are involved in (poly)Ub interactions with the majority of Ub-binding proteins, their sequestration at the Ub-Ub interface renders the closed conformation of polyUb binding incompetent. Thus the existence of open conformation(s) and the interdomain motions opening and closing the Ub-Ub interface is critical for the recognition of Lys48-linked polyUb by its receptors. Knowledge of the conformational properties of a polyUb signal is essential for our understanding of its specific recognition by various Ub-receptors. Despite their functional importance, open states of Lys48-linked chains are poorly characterized. Here we report a crystal structure of the open state of Lys48-linked di-Ub. Moreover, using NMR, we examined interactions of the open state of this chain (at pH4.5) with a Lys48-linkage-selective receptor, the UBA2 domain of a shuttle protein hHR23a. Our results show that di-Ub binds UBA2 in the same mode and with comparable affinity as the closed state. Our data suggest a mechanism for polyUb signal recognition, whereby Ub-binding proteins select specific conformations out of the available ensemble of polyUb chain conformations. This article is part of a Special Issue entitled: Ubiquitin Drug Discovery and Diagnostics.
-{{STRUCTURE_3ns8|  PDB=3ns8  |  SCENE=  }}
+Structural and biochemical studies of the open state of Lys48-linked diubiquitin.,Lai MY, Zhang D, Laronde-Leblanc N, Fushman D Biochim Biophys Acta. 2012 Nov;1823(11):2046-56. doi:, 10.1016/j.bbamcr.2012.04.003. Epub 2012 Apr 16. PMID:22542781<ref>PMID:22542781</ref>
-===Crystal structure of an open conformation of Lys48-linked diubiquitin at pH 7.5===
+From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
+</div>
-{{ABSTRACT_PUBMED_22542781}}
-==About this Structure==
-[[3ns8]] is a 2 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=3NS8 OCA].
 ==See Also==
 *[[Ubiquitin|Ubiquitin]]
+== References ==
+<references/>
+__TOC__
+</StructureSection>
 [[Category: Homo sapiens]]
-[[Category: Fushman, D.]]
+[[Category: Fushman, D]]
-[[Category: LaRonde-LeBlanc, N.]]
+[[Category: LaRonde-LeBlanc, N]]
-[[Category: Zhang, D.]]
+[[Category: Zhang, D]]
 [[Category: Diubiquitin]]
 [[Category: Isopeptide bond]]
 [[Category: Signaling protein]]