2F60

Crystal Structure of the Dihydrolipoamide Dehydrogenase (E3)-Binding Domain of Human E3-Binding Protein

2F60 の概要

• エントリーDOI: 10.2210/pdb2f60/pdb
• 関連するPDBエントリー: 2F5Z
• 分子名称: Pyruvate dehydrogenase protein X component, GLYCEROL (3 entities in total)
• 機能のキーワード: protein-binding protein, e3bd, protein binding
• 由来する生物種: Homo sapiens (human)
• 細胞内の位置: Mitochondrion matrix: O00330
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 7334.34

構造登録者

Brautigam, C.A.,Chuang, J.L.,Wynn, R.M.,Tomchick, D.R.,Machius, M.,Chuang, D.T. (登録日: 2005-11-28, 公開日: 2006-01-17, 最終更新日: 2023-08-23)

主引用文献

Brautigam, C.A.,Wynn, R.M.,Chuang, J.L.,Machius, M.,Tomchick, D.R.,Chuang, D.T.
Structural Insight into Interactions between Dihydrolipoamide Dehydrogenase (E3) and E3 Binding Protein of Human Pyruvate Dehydrogenase Complex.
Structure, 14:611-621, 2006

PubMed Abstract: The 9.5 MDa human pyruvate dehydrogenase complex (PDC) utilizes the specific dihydrolipoamide dehydrogenase (E3) binding protein (E3BP) to tether the essential E3 component to the 60-meric core of the complex. Here, we report crystal structures of the binding domain (E3BD) of human E3BP alone and in complex with human E3 at 1.6 angstroms and 2.2 angstroms, respectively. The latter structure shows that residues from E3BD contact E3 across its 2-fold axis, resulting in one E3BD binding site on the E3 homodimer. Negligible conformational changes occur in E3BD upon its high-affinity binding to E3. Modifications of E3BD residues at the center of the E3BD/E3 interface impede E3 binding far more severely than those of residues on the periphery, validating the "hot spot" paradigm for protein interactions. A cluster of disease-causing E3 mutations located near the center of the E3BD/E3 interface prevents the efficient recruitment of these E3 variants by E3BP into the PDC, leading to the dysfunction of the PDC catalytic machine.

PubMed: 16442803
DOI: 10.1016/j.str.2006.01.001

実験手法

X-RAY DIFFRACTION (1.55 Å)