4HXI

Crystal structure of KLHL3/Cul3 complex

4HXI の概要

• エントリーDOI: 10.2210/pdb4hxi/pdb
• 分子名称: Kelch-like protein 3, Cullin-3 (2 entities in total)
• 機能のキーワード: btb-back, protein-protein interaction, protein binding
• 由来する生物種: Homo sapiens (human); 詳細
• 細胞内の位置: Cytoplasm, cytoskeleton: Q9UH77; Nucleus: Q13618
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 76576.45

構造登録者

Ji, A.X.,Prive, G.G. (登録日: 2012-11-10, 公開日: 2013-03-13, 最終更新日: 2023-11-15)

主引用文献

Ji, A.X.,Prive, G.G.
Crystal structure of KLHL3 in complex with Cullin3.
Plos One, 8:e60445-e60445, 2013

PubMed Abstract: KLHL3 is a BTB-BACK-Kelch family protein that serves as a substrate adapter in Cullin3 (Cul3) E3 ubiquitin ligase complexes. KLHL3 is highly expressed in distal nephron tubules where it is involved in the regulation of electrolyte homeostasis and blood pressure. Mutations in KLHL3 have been identified in patients with inherited hypertension disorders, and several of the disease-associated mutations are located in the presumed Cul3 binding region. Here, we report the crystal structure of a complex between the KLHL3 BTB-BACK domain dimer and two copies of an N terminal fragment of Cul3. We use isothermal titration calorimetry to directly demonstrate that several of the disease mutations in the KLHL3 BTB-BACK domains disrupt the association with Cul3. Both the BTB and BACK domains contribute to the Cul3 interaction surface, and an extended model of the dimeric CRL3 complex places the two E2 binding sites in a suprafacial arrangement with respect to the presumed substrate-binding sites.

PubMed: 23573258
DOI: 10.1371/journal.pone.0060445

実験手法

X-RAY DIFFRACTION (3.513 Å)