6TBT

Crystal structure of the BCL6 BTB domain in complex with an Apt48 peptide

6TBT の概要

• エントリーDOI: 10.2210/pdb6tbt/pdb
• 分子名称: B-cell lymphoma 6 protein, Apt48 peptide, CHLORIDE ION, ... (7 entities in total)
• 機能のキーワード: bcl6, apt48, transcription
• 由来する生物種: Homo sapiens (Human); 詳細
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 32333.88

構造登録者

Zacharchenko, T.,Wright, S.C. (登録日: 2019-11-04, 公開日: 2021-10-13, 最終更新日: 2024-01-24)

主引用文献

Zacharchenko, T.,Kalverda, A.P.,Wright, S.C.
Structural basis of Apt48 inhibition of the BCL6 BTB domain.
Structure, 2021

PubMed Abstract: B cell lymphoma 6 (BCL6) is a transcriptional repressor that is deregulated in diffuse large B cell lymphoma, and the peptide aptamer, Apt48, inhibits BCL6 by an unknown mechanism. We report the crystal structure of BCL6 in complex with an Apt48 peptide, and show that Apt48 binds to a therapeutically uncharacterized region at the bottom of the BCL6 BTB domain. We show that the corepressor binding site of the BTB domain may be divided conceptually into two low-affinity, peptide-binding regions. An upper region, the lateral groove, binds peptides in robust three-dimensional conformations, whereas a lower binding site is permissive to less-specific interactions. We show that, even with little sequence specificity, the interactions of the lower region are required for the high-affinity binding of the SMRT corepressor and other peptides to the BTB domain. This has relevance for the design of new BCL6 inhibitors and for understanding the evolution of corepressor interactions with the BTB domain.

PubMed: 34774129
DOI: 10.1016/j.str.2021.10.010

実験手法

X-RAY DIFFRACTION (1.63 Å)