6KTO

Crystal structure of human SHLD3-C-REV7-O-REV7-SHLD2 complex

6KTO の概要

• エントリーDOI: 10.2210/pdb6kto/pdb
• 分子名称: Mitotic spindle assembly checkpoint protein MAD2B, Shieldin complex subunit 3, Shieldin complex subunit 2 (3 entities in total)
• 機能のキーワード: shieldin, complex, conformational dimer, nhej, replication
• 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: 65731.15

構造登録者

Liang, L.,Yin, Y. (登録日: 2019-08-28, 公開日: 2020-04-29, 最終更新日: 2023-11-22)

主引用文献

Liang, L.,Feng, J.,Zuo, P.,Yang, J.,Lu, Y.,Yin, Y.
Molecular basis for assembly of the shieldin complex and its implications for NHEJ.
Nat Commun, 11:1972-1972, 2020

PubMed Abstract: Shieldin, including SHLD1, SHLD2, SHLD3 and REV7, functions as a bridge linking 53BP1-RIF1 and single-strand DNA to suppress the DNA termini nucleolytic resection during non-homologous end joining (NHEJ). However, the mechanism of shieldin assembly remains unclear. Here we present the crystal structure of the SHLD3-REV7-SHLD2 ternary complex and reveal an unexpected C (closed)-REV7-O (open)-REV7 conformational dimer mediated by SHLD3. We show that SHLD2 interacts with O-REV7 and the N-terminus of SHLD3 by forming β sheet sandwich. Disruption of the REV7 conformational dimer abolishes the assembly of shieldin and impairs NHEJ efficiency. The conserved FXPWFP motif of SHLD3 binds to C-REV7 and blocks its binding to REV1, which excludes shieldin from the REV1/Pol ζ translesion synthesis (TLS) complex. Our study reveals the molecular architecture of shieldin assembly, elucidates the structural basis of the REV7 conformational dimer, and provides mechanistic insight into orchestration between TLS and NHEJ.

PubMed: 32332881
DOI: 10.1038/s41467-020-15879-5

実験手法

X-RAY DIFFRACTION (3.44976331487 Å)