4asc

From Proteopedia

(Difference between revisions)

Current revision

Crystal structure of the Kelch domain of human KBTBD5

Structural highlights

4asc is a 1 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 1.78Å
Ligands:	,
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Disease

KLH40_HUMAN Severe congenital nemaline myopathy. The disease is caused by variants affecting the gene represented in this entry.

Function

KLH40_HUMAN Substrate-specific adapter of a BCR (BTB-CUL3-RBX1) E3 ubiquitin ligase complex that acts as a key regulator of skeletal muscle development (PubMed:23746549). The BCR(KLHL40) complex acts by mediating ubiquitination and degradation of TFDP1, thereby regulating the activity of the E2F:DP transcription factor complex (By similarity). Promotes stabilization of LMOD3 by acting as a negative regulator of LMOD3 ubiquitination; the molecular process by which it negatively regulates ubiquitination of LMOD3 is however unclear (By similarity).[UniProtKB:Q9D783]^[1]

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^[2]

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

References

↑ Ravenscroft G, Miyatake S, Lehtokari VL, Todd EJ, Vornanen P, Yau KS, Hayashi YK, Miyake N, Tsurusaki Y, Doi H, Saitsu H, Osaka H, Yamashita S, Ohya T, Sakamoto Y, Koshimizu E, Imamura S, Yamashita M, Ogata K, Shiina M, Bryson-Richardson RJ, Vaz R, Ceyhan O, Brownstein CA, Swanson LC, Monnot S, Romero NB, Amthor H, Kresoje N, Sivadorai P, Kiraly-Borri C, Haliloglu G, Talim B, Orhan D, Kale G, Charles AK, Fabian VA, Davis MR, Lammens M, Sewry CA, Manzur A, Muntoni F, Clarke NF, North KN, Bertini E, Nevo Y, Willichowski E, Silberg IE, Topaloglu H, Beggs AH, Allcock RJ, Nishino I, Wallgren-Pettersson C, Matsumoto N, Laing NG. Mutations in KLHL40 are a frequent cause of severe autosomal-recessive nemaline myopathy. Am J Hum Genet. 2013 Jul 11;93(1):6-18. PMID:23746549 doi:10.1016/j.ajhg.2013.05.004
↑ 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 Disease
3 Function
4 Publication Abstract from PubMed
5 See Also
6 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

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

@@ Line 3: / Line 3: @@
 <StructureSection load='4asc' size='340' side='right'caption='[[4asc]], [[Resolution|resolution]] 1.78&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[4asc]] is a 1 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=4ASC OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4ASC FirstGlance]. <br>
+<table><tr><td colspan='2'>[[4asc]] is a 1 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=4ASC OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4ASC FirstGlance]. <br>
-</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</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]] 1.78&#8491;</td></tr>
-<tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=CSO:S-HYDROXYCYSTEINE'>CSO</scene></td></tr>
+<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CSO:S-HYDROXYCYSTEINE'>CSO</scene>, <scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene></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=4asc FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4asc OCA], [http://pdbe.org/4asc PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4asc RCSB], [http://www.ebi.ac.uk/pdbsum/4asc PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4asc 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=4asc FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4asc OCA], [https://pdbe.org/4asc PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4asc RCSB], [https://www.ebi.ac.uk/pdbsum/4asc PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4asc ProSAT]</span></td></tr>
 </table>
+== Disease ==
+[https://www.uniprot.org/uniprot/KLH40_HUMAN KLH40_HUMAN] Severe congenital nemaline myopathy. The disease is caused by variants affecting the gene represented in this entry.
+== Function ==
+[https://www.uniprot.org/uniprot/KLH40_HUMAN KLH40_HUMAN] Substrate-specific adapter of a BCR (BTB-CUL3-RBX1) E3 ubiquitin ligase complex that acts as a key regulator of skeletal muscle development (PubMed:23746549). The BCR(KLHL40) complex acts by mediating ubiquitination and degradation of TFDP1, thereby regulating the activity of the E2F:DP transcription factor complex (By similarity). Promotes stabilization of LMOD3 by acting as a negative regulator of LMOD3 ubiquitination; the molecular process by which it negatively regulates ubiquitination of LMOD3 is however unclear (By similarity).[UniProtKB:Q9D783]<ref>PMID:23746549</ref>
 <div style="background-color:#fffaf0;">
 == Publication Abstract from PubMed ==
@@ Line 24: / Line 28: @@
 __TOC__
 </StructureSection>
-[[Category: Human]]
+[[Category: Homo sapiens]]
 [[Category: Large Structures]]
-[[Category: Arrowsmith, C H]]
+[[Category: Arrowsmith CH]]
-[[Category: Ayinampudi, V]]
+[[Category: Ayinampudi V]]
-[[Category: Bountra, C]]
+[[Category: Bountra C]]
-[[Category: Bullock, A N]]
+[[Category: Bullock AN]]
-[[Category: Canning, P]]
+[[Category: Canning P]]
-[[Category: Delft, F von]]
+[[Category: Edwards AM]]
-[[Category: Edwards, A M]]
+[[Category: Krojer T]]
-[[Category: Krojer, T]]
+[[Category: Raynor J]]
-[[Category: Raynor, J]]
+[[Category: Strain-Damerell C]]
-[[Category: Structural genomic]]
+[[Category: Von Delft F]]
-[[Category: Strain-Damerell, C]]
-[[Category: Cytoskeleton]]
-[[Category: Kelch repeat]]
-[[Category: Protein binding]]

4asc

From Proteopedia

Current revision

Crystal structure of the Kelch domain of human KBTBD5

Structural highlights

Disease

Function

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

Views

Personal tools

Navigation

Search

Toolbox