7ZEL

Human SLFN11 dimer apoenzyme

7ZEL の概要

• エントリーDOI: 10.2210/pdb7zel/pdb
• EMDBエントリー: 14690
• 分子名称: Schlafen family member 11, ZINC ION, MAGNESIUM ION (3 entities in total)
• 機能のキーワード: trna endonuclease, single-strand dna binding protein, hydrolase
• 由来する生物種: Homo sapiens (human)
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 212595.26

構造登録者

Metzner, F.J.,Kugler, M.,Wenzl, S.J.,Lammens, K. (登録日: 2022-03-31, 公開日: 2022-09-28, 最終更新日: 2024-07-24)

主引用文献

Metzner, F.J.,Wenzl, S.J.,Kugler, M.,Krebs, S.,Hopfner, K.P.,Lammens, K.
Mechanistic understanding of human SLFN11.
Nat Commun, 13:5464-5464, 2022

PubMed Abstract: Schlafen 11 (SLFN11) is an interferon-inducible antiviral restriction factor with tRNA endoribonuclease and DNA binding functions. It is recruited to stalled replication forks in response to replication stress and inhibits replication of certain viruses such as the human immunodeficiency virus 1 (HIV-1) by modulating the tRNA pool. SLFN11 has been identified as a predictive biomarker in cancer, as its expression correlates with a beneficial response to DNA damage inducing anticancer drugs. However, the mechanism and interdependence of these two functions are largely unknown. Here, we present cryo-electron microscopy (cryo-EM) structures of human SLFN11 in its dimeric apoenzyme state, bound to tRNA and in complex with single-strand DNA. Full-length SLFN11 neither hydrolyses nor binds ATP and the helicase domain appears in an autoinhibited state. Together with biochemical and structure guided mutagenesis studies, our data give detailed insights into the mechanism of endoribonuclease activity as well as suggestions on how SLFN11 may block stressed replication forks.

PubMed: 36115853
DOI: 10.1038/s41467-022-33123-0

実験手法

ELECTRON MICROSCOPY (2.8 Å)