6MDW

Mechanism of protease dependent DPC repair

6MDW の概要

• エントリーDOI: 10.2210/pdb6mdw/pdb
• 分子名称: SprT-like domain-containing protein Spartan, CITRATE ANION, ADENOSINE-5'-DIPHOSPHATE, ... (6 entities in total)
• 機能のキーワード: dpc repair protease, dna binding protein
• 由来する生物種: Homo sapiens (Human)
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 23521.90

構造登録者

Li, F.,Raczynska, J.,Chen, Z.,Yu, H. (登録日: 2018-09-05, 公開日: 2019-04-10, 最終更新日: 2023-10-11)

主引用文献

Li, F.,Raczynska, J.E.,Chen, Z.,Yu, H.
Structural Insight into DNA-Dependent Activation of Human Metalloprotease Spartan.
Cell Rep, 26:3336-3346.e4, 2019

PubMed Abstract: The DNA-dependent metalloprotease Spartan (SPRTN) cleaves DNA-protein crosslinks (DPCs) and protects cells from DPC-induced genome instability. Germline mutations of SPRTN are linked to human Ruijs-Aalfs syndrome (RJALS) characterized by progeria and early-onset hepatocellular carcinoma. The mechanism of DNA-mediated activation of SPRTN is not understood. Here, we report the crystal structure of the human SPRTN SprT domain bound to single-stranded DNA (ssDNA). Our structure reveals a Zn-binding sub-domain (ZBD) in SprT that shields its active site located in the metalloprotease sub-domain (MPD). The narrow catalytic groove between MPD and ZBD only permits cleavage of flexible substrates. The ZBD contains an ssDNA-binding site, with a DNA-base-binding pocket formed by aromatic residues. Mutations of ssDNA-binding residues diminish the protease activity of SPRTN. We propose that the ZBD contributes to the ssDNA specificity of SPRTN, restricts the access of globular substrates, and positions DPCs, which may need to be partially unfolded, for optimal cleavage.

PubMed: 30893605
DOI: 10.1016/j.celrep.2019.02.082

実験手法

X-RAY DIFFRACTION (1.5 Å)