2QC9

Mouse Notch 1 Ankyrin Repeat Intracellular Domain

2QC9 の概要

• エントリーDOI: 10.2210/pdb2qc9/pdb
• 分子名称: Notch 1 protein (2 entities in total)
• 機能のキーワード: beta-hydroxy asparagine, ankyrin repeat, factor inhibiting hif, transcription
• 由来する生物種: Mus musculus (house mouse)
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 46265.62

構造登録者

McDonough, M.A.,Schofield, C.J. (登録日: 2007-06-19, 公開日: 2008-03-04, 最終更新日: 2023-08-30)

主引用文献

Coleman, M.L.,McDonough, M.A.,Hewitson, K.S.,Coles, C.,Mecinovic, J.,Edelmann, M.,Cook, K.M.,Cockman, M.E.,Lancaster, D.E.,Kessler, B.M.,Oldham, N.J.,Ratcliffe, P.J.,Schofield, C.J.
Asparaginyl hydroxylation of the Notch ankyrin repeat domain by factor inhibiting hypoxia-inducible factor.
J.Biol.Chem., 282:24027-24038, 2007

PubMed Abstract: The stability and activity of hypoxia-inducible factor (HIF) are regulated by the post-translational hydroxylation of specific prolyl and asparaginyl residues. We show that the HIF asparaginyl hydroxylase, factor inhibiting HIF (FIH), also catalyzes hydroxylation of highly conserved asparaginyl residues within ankyrin repeat (AR) domains (ARDs) of endogenous Notch receptors. AR hydroxylation decreases the extent of ARD binding to FIH while not affecting signaling through the canonical Notch pathway. ARD proteins were found to efficiently compete with HIF for FIH-dependent hydroxylation. Crystallographic analyses of the hydroxylated Notch ARD (2.35A) and of Notch peptides bound to FIH (2.4-2.6A) reveal the stereochemistry of hydroxylation on the AR and imply that significant conformational changes are required in the ARD fold in order to enable hydroxylation at the FIH active site. We propose that ARD proteins function as natural inhibitors of FIH and that the hydroxylation status of these proteins provides another oxygen-dependent interface that modulates HIF signaling.

PubMed: 17573339
DOI: 10.1074/jbc.M704102200

実験手法

X-RAY DIFFRACTION (2.35 Å)