8A4I

Crystal structure of SALL4 zinc finger cluster 4 with AT-rich DNA

8A4I の概要

• エントリーDOI: 10.2210/pdb8a4i/pdb
• 分子名称: Sal-like protein 4, DNA (5'-D(*GP*AP*TP*AP*TP*TP*AP*AP*TP*AP*TP*C)-3'), ZINC ION, ... (5 entities in total)
• 機能のキーワード: sall4, at-rich dna, okihiro syndrome, transcription factor, stem cell, dna binding protein
• 由来する生物種: Mus musculus (house mouse); 詳細
• タンパク質・核酸の鎖数: 12
• 化学式量合計: 63141.39

構造登録者

Watson, J.A.,Pantier, R.,Jayachandran, U.,Chhatbar, K.,Alexander-Howden, B.,Kruusvee, V.,Prendecki, M.,Bird, A.,Cook, A.G. (登録日: 2022-06-11, 公開日: 2023-01-11, 最終更新日: 2024-05-01)

主引用文献

Watson, J.A.,Pantier, R.,Jayachandran, U.,Chhatbar, K.,Alexander-Howden, B.,Kruusvee, V.,Prendecki, M.,Bird, A.,Cook, A.G.
Structure of SALL4 zinc finger domain reveals link between AT-rich DNA binding and Okihiro syndrome.
Life Sci Alliance, 6:-, 2023

PubMed Abstract: Spalt-like 4 (SALL4) maintains vertebrate embryonic stem cell identity and is required for the development of multiple organs, including limbs. Mutations in SALL4 are associated with Okihiro syndrome, and SALL4 is also a known target of thalidomide. SALL4 protein has a distinct preference for AT-rich sequences, recognised by a pair of zinc fingers at the C-terminus. However, unlike many characterised zinc finger proteins, SALL4 shows flexible recognition with many different combinations of AT-rich sequences being targeted. SALL4 interacts with the NuRD corepressor complex which potentially mediates repression of AT-rich genes. We present a crystal structure of SALL4 C-terminal zinc fingers with an AT-rich DNA sequence, which shows that SALL4 uses small hydrophobic and polar side chains to provide flexible recognition in the major groove. Missense mutations reported in patients that lie within the C-terminal zinc fingers reduced overall binding to DNA but not the preference for AT-rich sequences. Furthermore, these mutations altered association of SALL4 with AT-rich genomic sites, providing evidence that these mutations are likely pathogenic.

PubMed: 36635047
DOI: 10.26508/lsa.202201588

実験手法

X-RAY DIFFRACTION (2.76 Å)