7ZF1

Structure of ubiquitinated FANCI in complex with FANCD2 and double-stranded DNA

7ZF1 の概要

• エントリーDOI: 10.2210/pdb7zf1/pdb
• EMDBエントリー: 14694
• 分子名称: Fanconi anemia group I protein, Fanconi anemia group D2 protein, Ubiquitin-60S ribosomal protein L40, ... (5 entities in total)
• 機能のキーワード: fanconi anemia, dna repair, ubiquitination, id2 complex, dna binding protein
• 由来する生物種: Homo sapiens (human); 詳細
• タンパク質・核酸の鎖数: 5
• 化学式量合計: 345679.90

構造登録者

Lemonidis, K.,Rennie, M.L.,Arkinson, C.,Streetley, J.,Clarke, M.,Chaugule, V.K.,Walden, H. (登録日: 2022-03-31, 公開日: 2022-11-16, 最終更新日: 2024-07-24)

主引用文献

Lemonidis, K.,Rennie, M.L.,Arkinson, C.,Chaugule, V.K.,Clarke, M.,Streetley, J.,Walden, H.
Structural and biochemical basis of interdependent FANCI-FANCD2 ubiquitination.
Embo J., 42:e111898-e111898, 2023

PubMed Abstract: Di-monoubiquitination of the FANCI-FANCD2 (ID2) complex is a central and crucial step for the repair of DNA interstrand crosslinks via the Fanconi anaemia pathway. While FANCD2 ubiquitination precedes FANCI ubiquitination, FANCD2 is also deubiquitinated at a faster rate than FANCI, which can result in a FANCI-ubiquitinated ID2 complex (I D2). Here, we present a 4.1 Å cryo-EM structure of I D2 complex bound to double-stranded DNA. We show that this complex, like ID2 and I D2 , is also in the closed ID2 conformation and clamps on DNA. The target lysine of FANCD2 (K561) becomes fully exposed in the I D2-DNA structure and is thus primed for ubiquitination. Similarly, FANCI's target lysine (K523) is also primed for ubiquitination in the ID2 -DNA complex. The I D2-DNA complex exhibits deubiquitination resistance, conferred by the presence of DNA and FANCD2. ID2 -DNA, on the other hand, can be efficiently deubiquitinated by USP1-UAF1, unless further ubiquitination on FANCI occurs. Therefore, FANCI ubiquitination effectively maintains FANCD2 ubiquitination in two ways: it prevents excessive FANCD2 deubiquitination within an I D2 -DNA complex, and it enables re-ubiquitination of FANCD2 within a transient, closed-on-DNA, I D2 complex.

PubMed: 36385258
DOI: 10.15252/embj.2022111898

実験手法

ELECTRON MICROSCOPY (4.14 Å)