4I6G

a vertebrate cryptochrome with FAD

4I6G の概要

• エントリーDOI: 10.2210/pdb4i6g/pdb
• 関連するPDBエントリー: 4I6E 4I6J
• 分子名称: Cryptochrome-2, FLAVIN-ADENINE DINUCLEOTIDE (3 entities in total)
• 機能のキーワード: cryptochrome, circadian clock, metabolite, photolyase fold, fad, fbxl3, periods, nucleus, transcription
• 由来する生物種: Mus musculus (mouse)
• 細胞内の位置: Cytoplasm: Q9R194
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 118949.19

構造登録者

Xing, W.,Busino, L.,Hinds, T.R.,Marionni, S.T.,Saifee, N.H.,Bush, M.F.,Pagano, M.,Zheng, N. (登録日: 2012-11-29, 公開日: 2013-03-13, 最終更新日: 2024-02-28)

主引用文献

Xing, W.,Busino, L.,Hinds, T.R.,Marionni, S.T.,Saifee, N.H.,Bush, M.F.,Pagano, M.,Zheng, N.
SCFFBXL3 ubiquitin ligase targets cryptochromes at their cofactor pocket.
Nature, 496:64-68, 2013

PubMed Abstract: The cryptochrome (CRY) flavoproteins act as blue-light receptors in plants and insects, but perform light-independent functions at the core of the mammalian circadian clock. To drive clock oscillations, mammalian CRYs associate with the Period proteins (PERs) and together inhibit the transcription of their own genes. The SCF(FBXL3) ubiquitin ligase complex controls this negative feedback loop by promoting CRY ubiquitination and degradation. However, the molecular mechanisms of their interactions and the functional role of flavin adenine dinucleotide (FAD) binding in CRYs remain poorly understood. Here we report crystal structures of mammalian CRY2 in its apo, FAD-bound and FBXL3-SKP1-complexed forms. Distinct from other cryptochromes of known structures, mammalian CRY2 binds FAD dynamically with an open cofactor pocket. Notably, the F-box protein FBXL3 captures CRY2 by simultaneously occupying its FAD-binding pocket with a conserved carboxy-terminal tail and burying its PER-binding interface. This novel F-box-protein-substrate bipartite interaction is susceptible to disruption by both FAD and PERs, suggesting a new avenue for pharmacological targeting of the complex and a multifaceted regulatory mechanism of CRY ubiquitination.

PubMed: 23503662
DOI: 10.1038/nature11964

実験手法

X-RAY DIFFRACTION (2.2 Å)