Kelch-like protein

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

↑ 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
↑ 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

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Michal Harel, Alexander Berchansky, Joel L. Sussman

[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

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