Kelch-like protein: Difference between revisions

From Proteopedia
Jump to navigation Jump to search
← Older edit
Joel L. Sussman (talk | contribs)
ConfirmAccount, Editor, Journal, Mutation, Print3D, Tester, Bureaucrats, Administrators
7,980 edits
No edit summary
Michal Harel (talk | contribs)
31,761 edits
No edit summary
 
(3 intermediate revisions by 2 users not shown)
Line 1: Line 1:
<StructureSection load='' size='450' side='right' caption='Human Kelch-like protein 1 (Keap1) Kelch domain (cyan) complex with NRF2 Neh2 peptide (green) and sulfate (PDB code [[1x2r]])' scene='70/706701/Cv/1'>
<StructureSection load='' size='450' side='right' caption='Human Kelch-like protein 1 (Keap1) Kelch domain (cyan) complex with NRF2 Neh2 peptide (green) and sulfate (PDB code [[1x2r]])' scene='70/706701/Cv/1'>
== Function ==
== Function ==
'''Kelch-like proteins''' (KLHL) contain multiple Kelch motifs.  This motif is about 50 residues long and forms a four-stranded β-sheet blade.  <scene name='70/706701/Cv/2'>Six to eight such blades form a circular β-propeller domain</scene>.  β-propellers are involved in protein-protein interactions.  The N-terminal of KLHL contains other protein domains like BTB (Broad-Tramtrack-Bric-a-brac) which is also involved in protein-protein interactions<ref>PMID:23676014</ref>.<br />
'''Kelch-like proteins''' (KLHL) contain multiple Kelch motifs.  This motif is about 50 residues long and forms a four-stranded β-sheet blade.  <scene name='70/706701/Cv/6'>Six to eight such blades form a circular β-propeller domain</scene>.  β-propellers are involved in protein-protein interactions.  The N-terminal of KLHL contains other protein domains like BTB (Broad-Tramtrack-Bric-a-brac) which is also involved in protein-protein interactions<ref>PMID:23676014</ref>.<br />
*'''KLHL1''' may play a role in organizing the actin cytoskeleton in brain cells.<br />
*'''KLHL2''' '''KLHL11''' is a component of the cullin-RING based E3 ubiquitin-protein ligase system.<br />
*'''KLHL2''' '''KLHL11''' is a component of the cullin-RING based E3 ubiquitin-protein ligase system.<br />
*'''KLHL3''' and '''KLHL7''' '''KLHL10''' are substrate-specific adapters of the cullin-RING based E3 ubiquitin-protein ligase system.<br />
*'''KLHL3''' and '''KLHL7''' '''KLHL10''' are substrate-specific adapters of the cullin-RING based E3 ubiquitin-protein ligase system.<br />
Line 16: Line 15:


== Structural highlights ==
== Structural highlights ==
The <scene name='70/706701/Cv/5'>interaction of Keap1 with Neh2 is through the first Glu in the latter's ETGE motif</scene><ref>PMID:16507366</ref>. <scene name='70/706701/Cv/3'>All interactions of Keap1 with Neh2</scene>. Water molecules shown as red spheres.
The <scene name='70/706701/Cv/7'>interaction of Keap1 with Neh2 is through the first Glu in the latter's ETGE motif</scene><ref>PMID:16507366</ref>. <scene name='70/706701/Cv/8'>All interactions of Keap1 with Neh2</scene>. Water molecules shown as red spheres.
 
</StructureSection>


== 3D Structures of Kelch-like protein ==
== 3D Structures of Kelch-like protein ==
[[Kelch-like protein 3D structures]]


Updated on {{REVISIONDAY2}}-{{MONTHNAME|{{REVISIONMONTH}}}}-{{REVISIONYEAR}}
</StructureSection>
{{#tree:id=OrganizedByTopic|openlevels=0|
 
*Kelch-like protein 1
 
**[[4xmb]] – hKLHL1 Kelch domain + NRF2 activator - human <br />
**[[5cgj]] – mKLHL1 Kelch domain + NRF2 activator - mouse <br />
 
*Kelch-like protein 2
 
**[[2xn4]] – hKLHL2 Kelch domain  <br />
 
*Kelch-like protein 3
 
**[[4chb]], [[4ch9]], [[5nkp]] – hKLHL3 Kelch domain + serine/threonine protein kinas WNK4 peptide <br />
**[[4hxi]] – hKLHL3 BTB-BACK domain (mutant) + cullin-3 N terminal <br />
 
*Kelch-like protein 4
 
**[[2eqx]] – hKLHL4 BACK domain - NMR <br />
 
*Kelch-like protein 5
 
**[[4asc]] – hKLHL5 Kelch domain  <br />
 
*Kelch-like protein 7
 
**[[3ii7]] – hKLHL7 Kelch domain  <br />
 
*Kelch-like protein 10
 
**[[2woz]] – KLHL10 Kelch domain - rat <br />
 
*Kelch-like protein 11
 
**[[3i3n]] – hKLHL11 BTB-BACK domain <br />
**[[4ap2]], [[4apf]] – hKLHL11 BTB-BACK domain + cullin-3 N terminal <br />
 
*Kelch-like protein 12
 
**[[2vpj]] – hKLHL12 Kelch domain  <br />
 
*Kelch-like protein 16 (gigaxonin)
 
**[[3hve]] – hKLHL16  <br />
**[[2ppi]] – hKLHL16 BTB domain  <br />
 
*Kelch-like protein 19 (kelch-like ECH-associated protein 1; Keap1)
 
**[[1u6d]], [[1zgk]], [[4ifj]] – hKeap1 Kelch domain  <br />
**[[3zgd]] – hKeap1 Kelch domain (mutant) <br />
**[[4cxi]], [[4cxj]] – hKeap1 BTB domain (mutant) <br />
**[[1x2j]] – mKeap1 Kelch domain  <br />
 
*Keap1 complex with peptide
 
**[[1x2r]] – mKeap1 Kelch domain + NRF2 Neh2 peptide <br />
**[[2z32]] – mKeap1 Kelch domain + prothymosin a peptide <br />
**[[3ade]], [[3wdz]] – mKeap1 Kelch domain + sequestosome-1 peptide <br />
**[[2dyh]] – mKeap1 Kelch domain + NRF2 residues 22-36 <br />
**[[3wn7]] – mKeap1 Kelch domain + NRF2 residues 17-51 <br />
**[[4ifl]], [[2flu]], [[3zgc]] – hKeap1 Kelch domain + NRF2 Neh2 peptide <br />
**[[5nlb]] – hKeap1 BTB+ 3-BOX domains + CUL-3 <br />
**[[5f72]] – hKLHL1 Kelch domain + antibody  <br />
**[[5x54]] – hKLHL1 Kelch domain + tetrapeptide  <br />
 
*Keap1 complex with small molecule
 
**[[3vng]], [[3vnh]] – hKeap1 Kelch domain + oxadiazole derivative <br />
**[[4ifn]] – hKeap1 Kelch domain + quinoline derivative <br />
**[[4l7b]], [[4l7c]], [[4l7d]] [[4n1b]] – hKeap1 Kelch domain (mutant) + quinoline derivative <br />
**[[4in4]], [[4zy3]], [[5fnq]], [[5fnr]], [[5fns]], [[5fnt]], [[5fnu]], [[5fzj]], [[5fzn]] – hKeap1 Kelch domain + inhibitor <br />
**[[4iqk]], [[4n1b]] – hKeap1 Kelch domain (mutant) + inhibitor <br />
**[[4cxt]] – hKeap1 BTB domain (mutant) + antagonist<br />
**[[5dad]], [[5daf]] – hKeap1 BTB domain + activator  <br />
 
}}
 
 


== References ==
== References ==
<references/>
<references/>
[[Category:Topic Page]]
[[Category:Topic Page]]

Latest revision as of 12:56, 8 September 2019

Function

Kelch-like proteins (KLHL) contain multiple Kelch motifs. This motif is about 50 residues long and forms a four-stranded β-sheet blade. . β-propellers are involved in protein-protein interactions. The N-terminal of KLHL contains other protein domains like BTB (Broad-Tramtrack-Bric-a-brac) which is also involved in protein-protein interactions[1].

  • KLHL2 KLHL11 is a component of the cullin-RING based E3 ubiquitin-protein ligase system.
  • KLHL3 and KLHL7 KLHL10 are substrate-specific adapters of the cullin-RING based E3 ubiquitin-protein ligase system.
  • KLHL12 may play a role in collagen export.
  • KLHL16 or gigaxonin plays a role in neurofilament architecture.
  • KLHL19 (Keap1) interacts with the Neh2 peptide of NRF2.

Disease

Somatic mutations in Keap1 were found in lung cancer patients.

Relevance

NRF2 is a regulator of antioxidant response, hence Keap1 is investigated as a drug target.

Structural highlights

The [2]. . Water molecules shown as red spheres.

3D Structures of Kelch-like protein

Kelch-like protein 3D structures


Human Kelch-like protein 1 (Keap1) Kelch domain (cyan) complex with NRF2 Neh2 peptide (green) and sulfate (PDB code 1x2r)

Drag the structure with the mouse to rotate

ReferencesReferences

  1. ↑ Dhanoa BS, Cogliati T, Satish AG, Bruford EA, Friedman JS. Update on the Kelch-like (KLHL) gene family. Hum Genomics. 2013 May 15;7:13. doi: 10.1186/1479-7364-7-13. PMID:23676014 doi:http://dx.doi.org/10.1186/1479-7364-7-13
  2. ↑ Padmanabhan B, Tong KI, Ohta T, Nakamura Y, Scharlock M, Ohtsuji M, Kang MI, Kobayashi A, Yokoyama S, Yamamoto M. Structural basis for defects of Keap1 activity provoked by its point mutations in lung cancer. Mol Cell. 2006 Mar 3;21(5):689-700. PMID:16507366 doi:10.1016/j.molcel.2006.01.013

Proteopedia Page Contributors and Editors (what is this?)Proteopedia Page Contributors and Editors (what is this?)

Michal Harel, Alexander Berchansky, Joel L. Sussman
Retrieved from "https://proteopedia.openfox.io/wiki/index.php?title=Kelch-like_protein&oldid=3088154"