Protein Structure and Function Laboratory, Lincoln's Inn Fields Laboratories of the London Research Institute, Cancer Research UK, London Research Institute, London, UK.
Nat Struct Mol Biol. 2010 Mar;17(3):294-8. doi: 10.1038/nsmb.1759. Epub 2010 Feb 14.
The Fanconi anemia (FA) pathway is activated in response to DNA damage, leading to monoubiquitination of the substrates FANCI and FANCD2 by the FA core complex. Here we report the crystal structure of FANCL, the catalytic subunit of the FA core complex, at 3.2 A. The structure reveals an architecture fundamentally different from previous sequence-based predictions. The molecule is composed of an N-terminal E2-like fold, which we term the ELF domain, a novel double-RWD (DRWD) domain, and a C-terminal really interesting new gene (RING) domain predicted to facilitate E2 binding. Binding assays show that the DRWD domain, but not the ELF domain, is responsible for substrate binding.
范可尼贫血（FA）途径在 DNA 损伤时被激活，导致 FA 核心复合物对底物 FANCI 和 FANCD2 的单泛素化。在这里，我们报告了 FA 核心复合物的催化亚基 FANCL 的晶体结构，分辨率为 3.2Å。该结构揭示了一种与以前基于序列的预测完全不同的结构。该分子由一个 N 端的 E2 样折叠组成，我们称之为 ELF 结构域，一个新的双 RWD（DRWD）结构域，以及一个 C 端的真正有趣的新基因（RING）结构域，预计可以促进 E2 结合。结合实验表明，是 DRWD 结构域，而不是 ELF 结构域，负责底物结合。
