5WRS

Crystal Structure of Fam20A in complex with ATP

5WRS の概要

• エントリーDOI: 10.2210/pdb5wrs/pdb
• 関連するPDBエントリー: 5WRR
• 分子名称: Pseudokinase FAM20A, 2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose, 2-acetamido-2-deoxy-beta-D-glucopyranose, ... (4 entities in total)
• 機能のキーワード: secretory pathway pseudokinase, transferase
• 由来する生物種: Homo sapiens (Human)
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 103161.63

構造登録者

Zhu, Q. (登録日: 2016-12-03, 公開日: 2017-05-03, 最終更新日: 2024-10-16)

主引用文献

Cui, J.,Zhu, Q.,Zhang, H.,Cianfrocco, M.A.,Leschziner, A.E.,Dixon, J.E.,Xiao, J.
Structure of Fam20A reveals a pseudokinase featuring a unique disulfide pattern and inverted ATP-binding
Elife, 6:-, 2017

PubMed Abstract: Mutations in cause tooth enamel defects known as Amelogenesis Imperfecta (AI) and renal calcification. We previously showed that Fam20A is a secretory pathway pseudokinase and allosterically activates the physiological casein kinase Fam20C to phosphorylate secreted proteins important for biomineralization (Cui et al., 2015). Here we report the nucleotide-free and ATP-bound structures of Fam20A. Fam20A exhibits a distinct disulfide bond pattern mediated by a unique insertion region. Loss of this insertion due to abnormal mRNA splicing interferes with the structure and function of Fam20A, resulting in AI. Fam20A binds ATP in the absence of divalent cations, and strikingly, ATP is bound in an inverted orientation compared to other kinases. Fam20A forms a dimer in the crystal, and residues in the dimer interface are critical for Fam20C activation. Together, these results provide structural insights into the function of Fam20A and shed light on the mechanism by which Fam20A mutations cause disease.

PubMed: 28432788
DOI: 10.7554/eLife.23990

実験手法

X-RAY DIFFRACTION (2.75 Å)