PROTAC-induced protein structural dynamics in targeted protein degradation.

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Tác giả: Chia-En A Chang, Ta I Hung, Kingsley Y Wu

Ngôn ngữ: eng

Ký hiệu phân loại: 668.43 Protein plastics

Thông tin xuất bản: England : eLife , 2025

Mô tả vật lý:

Bộ sưu tập: NCBI

ID: 681727

 PROteolysis TArgeting Chimeras (PROTACs) are small molecules that induce target protein degradation via the ubiquitin-proteasome system. PROTACs recruit the target protein and E3 ligase
  a critical first step is forming a ternary complex. However, while the formation of a ternary complex is crucial, it may not always guarantee successful protein degradation. The dynamics of the PROTAC-induced degradation complex play a key role in ubiquitination and subsequent degradation. In this study, we computationally modelled protein complex structures and dynamics associated with a series of PROTACs featuring different linkers to investigate why these PROTACs, all of which formed ternary complexes with Cereblon (CRBN) E3 ligase and the target protein bromodomain-containing protein 4 (BRD4
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