3DVG

Crystal structure of K63-specific fab Apu.3A8 bound to K63-linked di-ubiquitin

3DVG の概要

• エントリーDOI: 10.2210/pdb3dvg/pdb
• 関連するPDBエントリー: 3DVN
• 分子名称: Human IgG1 fab fragment light chain, Human IgG1 fab fragment heavy chain, Ubiquitin D77, ... (5 entities in total)
• 機能のキーワード: di-ubiquitin, fab fragment, antibody, nucleus, phosphoprotein, ribosomal protein, immune system
• 由来する生物種: Homo sapiens (Human); 詳細
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 66183.13

構造登録者

Hymowitz, S.G. (登録日: 2008-07-18, 公開日: 2008-09-30, 最終更新日: 2024-10-09)

主引用文献

Newton, K.,Matsumoto, M.L.,Wertz, I.E.,Kirkpatrick, D.S.,Lill, J.R.,Tan, J.,Dugger, D.,Gordon, N.,Sidhu, S.S.,Fellouse, F.A.,Komuves, L.,French, D.M.,Ferrando, R.E.,Lam, C.,Compaan, D.,Yu, C.,Bosanac, I.,Hymowitz, S.G.,Kelley, R.F.,Dixit, V.M.
Ubiquitin chain editing revealed by polyubiquitin linkage-specific antibodies.
Cell(Cambridge,Mass.), 134:668-678, 2008

PubMed Abstract: Posttranslational modification of proteins with polyubiquitin occurs in diverse signaling pathways and is tightly regulated to ensure cellular homeostasis. Studies employing ubiquitin mutants suggest that the fate of polyubiquitinated proteins is determined by which lysine within ubiquitin is linked to the C terminus of an adjacent ubiquitin. We have developed linkage-specific antibodies that recognize polyubiquitin chains joined through lysine 63 (K63) or 48 (K48). A cocrystal structure of an anti-K63 linkage Fab bound to K63-linked diubiquitin provides insight into the molecular basis for specificity. We use these antibodies to demonstrate that RIP1, which is essential for tumor necrosis factor-induced NF-kappaB activation, and IRAK1, which participates in signaling by interleukin-1beta and Toll-like receptors, both undergo polyubiquitin editing in stimulated cells. Both kinase adaptors initially acquire K63-linked polyubiquitin, while at later times K48-linked polyubiquitin targets them for proteasomal degradation. Polyubiquitin editing may therefore be a general mechanism for attenuating innate immune signaling.

PubMed: 18724939
DOI: 10.1016/j.cell.2008.07.039

実験手法

X-RAY DIFFRACTION (2.6 Å)