2FTU

solution structure of domain 3 of RAP

2FTU の概要

• エントリーDOI: 10.2210/pdb2ftu/pdb
• 関連するPDBエントリー: 2FFT 2FFV
• 分子名称: Alpha-2-macroglobulin receptor-associated protein, domain 3 (1 entity in total)
• 機能のキーワード: domain 3; rap; receptor-associated protein, lipid binding protein
• 由来する生物種: Homo sapiens (human)
• 細胞内の位置: Endoplasmic reticulum: P30533
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 13881.46

構造登録者

Lee, D.,Walsh, J.D.,Wang, Y.-X. (登録日: 2006-01-24, 公開日: 2006-05-09, 最終更新日: 2024-05-29)

主引用文献

Lee, D.,Walsh, J.D.,Mikhailenko, I.,Yu, P.,Migliorini, M.,Wu, Y.,Krueger, S.,Curtis, J.E.,Harris, B.,Lockett, S.,Blacklow, S.C.,Strickland, D.K.,Wang, Y.X.
RAP uses a histidine switch to regulate its interaction with LRP in the ER and Golgi.
Mol.Cell, 22:423-430, 2006

PubMed Abstract: The receptor associated protein (RAP) is an antagonist and molecular chaperone that binds tightly to low-density lipoprotein receptor family members in the endoplasmic reticulum (ER). After escorting these receptors to the Golgi, RAP dissociates from the receptors. The molecular mechanism of the dissociation has been unknown until now. The solution structure of RAP-D3 domain presented here reveals a striking increase in positively charged residues on the surface of this RAP domain due to protonation of solvent-exposed histidine sidechains as the pH is reduced from a near neutral pH of the ER to the acidic pH of the Golgi. Structure-based mutagenesis studies in vitro and in cells confirm that the protonation of histidine residues as a consequence of the pH changes modulate the binding/release of RAP from LRP. This histidine switch may serve as a general mechanism for regulating cell trafficking events.

PubMed: 16678114
DOI: 10.1016/j.molcel.2006.04.011

実験手法

SOLUTION NMR