6OQ1

Crystal Structure of Branched K11/K48-Linked Tri-Ubiquitin

6OQ1 の概要

• エントリーDOI: 10.2210/pdb6oq1/pdb
• 分子名称: Ubiquitin, ... (4 entities in total)
• 機能のキーワード: signaling protein
• 由来する生物種: Homo sapiens (Human); 詳細
• タンパク質・核酸の鎖数: 6
• 化学式量合計: 51807.17

構造登録者

Boughton, A.J.,Fushman, D. (登録日: 2019-04-25, 公開日: 2019-10-23, 最終更新日: 2024-10-23)

主引用文献

Boughton, A.J.,Krueger, S.,Fushman, D.
Branching via K11 and K48 Bestows Ubiquitin Chains with a Unique Interdomain Interface and Enhanced Affinity for Proteasomal Subunit Rpn1.
Structure, 28:29-43.e6, 2020

PubMed Abstract: Post-translational substrate modification with ubiquitin is essential for eukaryotic cellular signaling. Polymeric ubiquitin chains are assembled with specific architectures, which convey distinct signaling outcomes depending on the linkages involved. Recently, branched K11/K48-linked polyubiquitins were shown to enhance proteasomal degradation during mitosis. To better understand the underlying structural mechanisms, we determined the crystal and NMR structures of branched K11/K48-linked tri-ubiquitin and discovered a previously unobserved interdomain interface between the distal ubiquitins. Small-angle neutron scattering and site-directed mutagenesis corroborated the presence of this interface, which we hypothesized to be influential in the physiological role of branched K11/K48-linked chains. Yet, experiments probing polyubiquitin interactions-deubiquitination assays, binding to proteasomal shuttle hHR23A-showed negligible differences between branched K11/K48-linked tri-ubiquitin and related di-ubiquitins. However, significantly stronger binding affinity for branched K11/K48-linked tri-ubiquitin was observed with proteasomal subunit Rpn1, thereby suggesting a functional impact of this interdomain interface and pinpointing the mechanistic site of enhanced degradation.

PubMed: 31677892
DOI: 10.1016/j.str.2019.10.008

実験手法

X-RAY DIFFRACTION (2.2 Å)