2MYM

Cullin3 - BTB interface: a novel target for stapled peptides

2MYM の概要

• エントリーDOI: 10.2210/pdb2mym/pdb
• 関連するPDBエントリー: 2MYL
• NMR情報: BMRB: 25457
• 分子名称: Cullin-3 (1 entity in total)
• 機能のキーワード: protein, protein binding
• 由来する生物種: Human (Homo sapiens)
• 細胞内の位置: Nucleus: Q13618
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 2445.81

構造登録者

Russo, L.,Palmieri, M.,Malgieri, G. (登録日: 2015-01-27, 公開日: 2015-04-22, 最終更新日: 2024-10-30)

主引用文献

de Paola, I.,Pirone, L.,Palmieri, M.,Balasco, N.,Esposito, L.,Russo, L.,Mazza, D.,Di Marcotullio, L.,Di Gaetano, S.,Malgieri, G.,Vitagliano, L.,Pedone, E.,Zaccaro, L.
Cullin3 - BTB Interface: A Novel Target for Stapled Peptides.
Plos One, 10:e0121149-e0121149, 2015

PubMed Abstract: Cullin3 (Cul3), a key factor of protein ubiquitination, is able to interact with dozens of different proteins containing a BTB (Bric-a-brac, Tramtrack and Broad Complex) domain. We here targeted the Cul3-BTB interface by using the intriguing approach of stabilizing the α-helical conformation of Cul3-based peptides through the "stapling" with a hydrocarbon cross-linker. In particular, by combining theoretical and experimental techniques, we designed and characterized stapled Cul3-based peptides embedding the helix 2 of the protein (residues 49-68). Intriguingly, CD and NMR experiments demonstrate that these stapled peptides were able to adopt the helical structure that the fragment assumes in the parent protein. We also show that some of these peptides were able to bind to the BTB of the tetrameric KCTD11, a substrate adaptor involved in HDAC1 degradation, with high affinity (~ 300-600 nM). Cul3-derived staple peptides are also able to bind the BTB of the pentameric KCTD5. Interestingly, the affinity of these peptides is of the same order of magnitude of that reported for the interaction of full-length Cul3 with some BTB containing proteins. Moreover, present data indicate that stapling endows these peptides with an increased serum stability. Altogether, these findings indicate that the designed stapled peptides can efficiently mimic protein-protein interactions and are potentially able to modulate fundamental biological processes involving Cul3.

PubMed: 25848797
DOI: 10.1371/journal.pone.0121149

実験手法

SOLUTION NMR