1OQJ

Crystal structure of the SAND domain from glucocorticoid modulatory element binding protein-1 (GMEB1)

1OQJ の概要

• エントリーDOI: 10.2210/pdb1oqj/pdb
• 関連するPDBエントリー: 1H5P
• 分子名称: Glucocorticoid Modulatory Element Binding protein-1, ZINC ION (3 entities in total)
• 機能のキーワード: sand domain, alpha-beta fold, kdwk motif, zinc-binding motif, dna binding protein
• 由来する生物種: Homo sapiens (human)
• 細胞内の位置: Nucleus: Q9Y692
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 22213.03

構造登録者

Surdo, P.L.,Bottomley, M.J.,Sattler, M.,Scheffzek, K. (登録日: 2003-03-10, 公開日: 2003-11-11, 最終更新日: 2024-02-14)

主引用文献

Surdo, P.L.,Bottomley, M.J.,Sattler, M.,Scheffzek, K.
Crystal structure and nuclear magnetic resonance analyses of the SAND domain from glucocorticoid modulatory element binding protein-1 reveals deoxyribonucleic acid and zinc binding regions
MOL.ENDOCRINOL., 17:1283-1295, 2003

PubMed Abstract: The glucocorticoid-modulatory element-binding proteins, GMEB1 and GMEB2, are ubiquitous, multifunctional DNA-binding proteins with important roles in the modulation of transcription upon steroid hormone activation. The GMEB proteins have intrinsic transactivation ability, but also control the glucocorticoid response via direct binding to the glucocorticoid receptor. They are also mandatory host proteins for Parvovirus replication. Here we present the 1.55 A resolution crystal structure of a central portion of GMEB1, encompassing its SAND domain, which shares 80% sequence identity with the GMEB2 SAND domain. We demonstrate that this domain, also present in numerous proteins implicated in chromatin-associated transcriptional regulation, is necessary and sufficient to bind the glucocorticoid-modulatory element (GME) DNA target. We use nuclear magnetic resonance (NMR) and binding studies to map the DNA recognition surface to an alpha-helical region exposing the conserved KDWK motif. Using site-directed mutagenesis, key residues for DNA binding are identified. In contrast to the previously determined NMR structure of the Sp100b SAND domain, we find that the GMEB1 SAND domain also comprises a zinc-binding motif. Although the zinc ion is not necessary for DNA binding, it is found to determine the C-terminal conformation of the GMEB1 SAND domain. We also show that homologous zinc-binding motifs exist in a subset of SAND domain proteins and probe the roles of this novel motif.

PubMed: 12702733
DOI: 10.1210/me.2002-0409

実験手法

X-RAY DIFFRACTION (1.55 Å)