4YJ0

Crystal structure of the DM domain of human DMRT1 bound to 25mer target DNA

4YJ0 の概要

• エントリーDOI: 10.2210/pdb4yj0/pdb
• 分子名称: Doublesex- and mab-3-related transcription factor 1, DNA (25-MER), ZINC ION, ... (4 entities in total)
• 機能のキーワード: transcription factor, protein-dna complex, double zn-finger, transcription
• 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: 40208.27

構造登録者

Murphy, M.W.,Lee, J.K.,Rojo, S.,Gearhart, M.D.,Kurahashi, K.,Banerjee, S.,Loeuille, G.,Bashamboo, A.,McElreavey, K.,Zarkower, D.,Aihara, H.,Bardwell, V.J. (登録日: 2015-03-02, 公開日: 2015-05-27, 最終更新日: 2024-06-19)

主引用文献

Murphy, M.W.,Lee, J.K.,Rojo, S.,Gearhart, M.D.,Kurahashi, K.,Banerjee, S.,Loeuille, G.A.,Bashamboo, A.,McElreavey, K.,Zarkower, D.,Aihara, H.,Bardwell, V.J.
An ancient protein-DNA interaction underlying metazoan sex determination.
Nat.Struct.Mol.Biol., 22:442-451, 2015

PubMed Abstract: DMRT transcription factors are deeply conserved regulators of metazoan sexual development. They share the DM DNA-binding domain, a unique intertwined double zinc-binding module followed by a C-terminal recognition helix, which binds a pseudopalindromic target DNA. Here we show that DMRT proteins use a unique binding interaction, inserting two adjacent antiparallel recognition helices into a widened DNA major groove to make base-specific contacts. Versatility in how specific base contacts are made allows human DMRT1 to use multiple DNA binding modes (tetramer, trimer and dimer). Chromatin immunoprecipitation with exonuclease treatment (ChIP-exo) indicates that multiple DNA binding modes also are used in vivo. We show that mutations affecting residues crucial for DNA recognition are associated with an intersex phenotype in flies and with male-to-female sex reversal in humans. Our results illuminate an ancient molecular interaction underlying much of metazoan sexual development.

PubMed: 26005864
DOI: 10.1038/nsmb.3032

実験手法

X-RAY DIFFRACTION (3.814 Å)