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4ap2

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Crystal structure of the human KLHL11-Cul3 complex at 2.8A resolution

Structural highlights

4ap2 is a 2 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	X-ray diffraction, Resolution 2.8Å
Ligands:	, ,
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

KLH11_HUMAN

Publication Abstract from PubMed

Cullin-RING ligases (CRLs) are multi-subunit E3 ubiquitin ligases that recruit substrate-specific adaptors to catalyze protein ubiquitylation. Cul3-based CRLs are uniquely associated with BTB adaptors that incorporate homodimerization, Cul3 assembly and substrate recognition into a single multi-domain protein, of which the best known are BTB-BACK-Kelch domain proteins including KEAP1. Cul3 assembly requires a BTB protein 3-box motif, analogous to the F-box and SOCS box motifs of other Cullin-based E3s. To define the molecular basis for this assembly and the overall architecture of the E3 we determined the crystal structures of the BTB-BACK domains of KLHL11 both alone and in complex with Cul3, along with the Kelch domain structures of KLHL2 (Mayven), KLHL7, KLHL12 and KBTBD5. We show that Cul3 interaction is dependent on an unique N-terminal extension sequence that packs against the 3-box in a hydrophobic groove centrally located between the BTB and BACK domains. Deletion of this N-terminal region results in a 30-fold loss in affinity. The presented data offer a model for the quaternary assembly of this E3 class that supports the bivalent capture of Nrf2 and reveals potential new sites for E3 inhibitor design.

Structural basis for Cul3 assembly with the BTB-Kelch family of E3 ubiquitin ligases.,Canning P, Cooper CD, Krojer T, Murray JW, Pike AC, Chaikuad A, Keates T, Thangaratnarajah C, Hojzan V, Marsden BD, Gileadi O, Knapp S, von Delft F, Bullock AN J Biol Chem. 2013 Jan 24. PMID:23349464^[1]

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

References

↑ Canning P, Cooper CD, Krojer T, Murray JW, Pike AC, Chaikuad A, Keates T, Thangaratnarajah C, Hojzan V, Marsden BD, Gileadi O, Knapp S, von Delft F, Bullock AN. Structural basis for Cul3 assembly with the BTB-Kelch family of E3 ubiquitin ligases. J Biol Chem. 2013 Jan 24. PMID:23349464 doi:http://dx.doi.org/10.1074/jbc.M112.437996

1 Structural highlights
2 Function
3 Publication Abstract from PubMed
4 See Also
5 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/4ap2"

@@ Line 1: / Line 1: @@
 ==Crystal structure of the human KLHL11-Cul3 complex at 2.8A resolution==
-<StructureSection load='4ap2' size='340' side='right' caption='[[4ap2]], [[Resolution|resolution]] 2.80&Aring;' scene=''>
+<StructureSection load='4ap2' size='340' side='right'caption='[[4ap2]], [[Resolution|resolution]] 2.80&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[4ap2]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4AP2 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4AP2 FirstGlance]. <br>
+<table><tr><td colspan='2'>[[4ap2]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4AP2 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4AP2 FirstGlance]. <br>
-</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=IOD:IODIDE+ION'>IOD</scene></td></tr>
+</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.8&#8491;</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=4ap2 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4ap2 OCA], [http://pdbe.org/4ap2 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4ap2 RCSB], [http://www.ebi.ac.uk/pdbsum/4ap2 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4ap2 ProSAT]</span></td></tr>
+<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=IOD:IODIDE+ION'>IOD</scene></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=4ap2 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4ap2 OCA], [https://pdbe.org/4ap2 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4ap2 RCSB], [https://www.ebi.ac.uk/pdbsum/4ap2 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4ap2 ProSAT]</span></td></tr>
 </table>
-== Disease ==
-[[http://www.uniprot.org/uniprot/CUL3_HUMAN CUL3_HUMAN]] Pseudohypoaldosteronism type 2E. Defects in CUL3 are the cause of Pseudohypoaldosteronism type 2E (PHA2E) [MIM:[http://omim.org/entry/614496 614496]]. An autosomal dominant disorder characterized by severe hypertension, hyperkalemia, hyperchloremia, hyperchloremic metabolic acidosis, and correction of physiologic abnormalities by thiazide diuretics.<ref>PMID:22266938</ref>
 == Function ==
-[[http://www.uniprot.org/uniprot/CUL3_HUMAN CUL3_HUMAN]] Core component of multiple cullin-RING-based BCR (BTB-CUL3-RBX1) E3 ubiquitin-protein ligase complexes which mediate the ubiquitination and subsequent proteasomal degradation of target proteins. As a scaffold protein may contribute to catalysis through positioning of the substrate and the ubiquitin-conjugating enzyme. The E3 ubiquitin-protein ligase activity of the complex is dependent on the neddylation of the cullin subunit and is inhibited by the association of the deneddylated cullin subunit with TIP120A/CAND1 (By similarity). The functional specificity of the BCR complex depends on the BTB domain-containing protein as the susbstrate recognition component. BCR(SPOP) is involved in ubiquitination of BMI1/PCGF4, H2AFY and DAXX, and probably GLI2 or GLI3. BCR(KLHL9-KLHL13) controls the dynamic behavior of AURKB on mitotic chromosomes and thereby coordinates faithful mitotic progression and completion of cytokinesis. BCR(KLHL12) is involved in ER-Golgi transport by regulating the size of COPII coats, thereby playing a key role in collagen export, which is required for embryonic stem (ES) cells division: BCR(KLHL12) acts by mediating monoubiquitination of SEC31 (SEC31A or SEC31B). BCR(KLHL3) acts as a regulator of ion transport in the distal nephron; possibly by mediating ubiquitination of SLC12A3/NCC. Involved in ubiquitination of cyclin E and of cyclin D1 (in vitro) thus involved in regulation of G1/S transition.<ref>PMID:10500095</ref> <ref>PMID:11311237</ref> <ref>PMID:15897469</ref> <ref>PMID:16524876</ref> <ref>PMID:17543862</ref> <ref>PMID:22358839</ref>
+[https://www.uniprot.org/uniprot/KLH11_HUMAN KLH11_HUMAN]
 <div style="background-color:#fffaf0;">
 == Publication Abstract from PubMed ==
@@ Line 22: / Line 21: @@
 ==See Also==
-*[[Cullin|Cullin]]
+*[[Cullin 3D structures|Cullin 3D structures]]
-*[[Kelch-like protein|Kelch-like protein]]
+*[[Kelch-like protein 3D structures|Kelch-like protein 3D structures]]
 == References ==
 <references/>
 __TOC__
 </StructureSection>
-[[Category: Human]]
+[[Category: Homo sapiens]]
-[[Category: Arrowsmith, C H]]
+[[Category: Large Structures]]
-[[Category: Ayinampudi, V]]
+[[Category: Arrowsmith CH]]
-[[Category: Bountra, C]]
+[[Category: Ayinampudi V]]
-[[Category: Bullock, A N]]
+[[Category: Bountra C]]
-[[Category: Canning, P]]
+[[Category: Bullock AN]]
-[[Category: Cooper, C D.O]]
+[[Category: Canning P]]
-[[Category: Delft, F Von]]
+[[Category: Cooper CDO]]
-[[Category: Edwards, A M]]
+[[Category: Edwards AM]]
-[[Category: Filippakopoulos, P]]
+[[Category: Filippakopoulos P]]
-[[Category: Krojer, T]]
+[[Category: Krojer T]]
-[[Category: Structural genomic]]
+[[Category: Von Delft F]]
-[[Category: Cell cycle]]
-[[Category: E3 ligase]]
-[[Category: Ubiquitination]]

4ap2

From Proteopedia

Current revision

Crystal structure of the human KLHL11-Cul3 complex at 2.8A resolution

Structural highlights

Function

Publication Abstract from PubMed

See Also

References

Contents

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