4PBD

Crystal structure of the N-terminal CS domain of human Shq1

4PBD の概要

• エントリーDOI: 10.2210/pdb4pbd/pdb
• 関連するPDBエントリー: 4PBD
• 分子名称: Protein SHQ1 homolog (2 entities in total)
• 機能のキーワード: cs domain, shq1, dyskerin, cbf5, telomerase, h/aca, protein binding
• 由来する生物種: Homo sapiens (Human)
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 12740.83

構造登録者

Singh, M.,Wang, Z.,Cascio, D.,Feigon, J. (登録日: 2014-04-12, 公開日: 2015-01-14, 最終更新日: 2024-11-06)

主引用文献

Singh, M.,Wang, Z.,Cascio, D.,Feigon, J.
Structure and Interactions of the CS Domain of Human H/ACA RNP Assembly Protein Shq1.
J.Mol.Biol., 427:807-823, 2015

PubMed Abstract: Shq1 is an essential protein involved in the early steps of biogenesis and assembly of H/ACA ribonucleoprotein particles (RNPs). Shq1 binds to dyskerin (Cbf5 in yeast) at an early step of H/ACA RNP assembly and is subsequently displaced by the H/ACA RNA. Shq1 contains an N-terminal CS and a C-terminal Shq1-specific domain (SSD). Dyskerin harbors many mutations associated with dyskeratosis congenita. Structures of yeast Shq1 SSD bound to Cbf5 revealed that only a subset of these mutations is in the SSD binding site, implicating another subset in the putative CS binding site. Here, we present the crystal structure of human Shq1 CS (hCS) and the nuclear magnetic resonance (NMR) and crystal structures of hCS containing a serine substitution for proline 22 that is associated with some prostate cancers. The structure of hCS is similar to yeast Shq1 CS domain (yCS) and consists of two β-sheets that form an immunoglobulin-like β-sandwich fold. The N-terminal affinity tag sequence AHHHHHH associates with a neighboring protein in the crystal lattice to form an extra β-strand. Deletion of this tag was required to get spectra suitable for NMR structure determination, while the tag was required for crystallization. NMR chemical shift perturbation (CSP) experiments with peptides derived from putative CS binding sites on dyskerin and Cbf5 revealed a conserved surface on CS important for Cbf5/dyskerin binding. A HADDOCK (high-ambiguity-driven protein-protein docking) model of a Shq1-Cbf5 complex that defines the position of CS domain in the pre-H/ACA RNP was calculated using the CSP data.

PubMed: 25553844
DOI: 10.1016/j.jmb.2014.12.012

実験手法

X-RAY DIFFRACTION (1.68 Å)