2L7B

NMR Structure of full length apoE3

2L7B の概要

• エントリーDOI: 10.2210/pdb2l7b/pdb
• NMR情報: BMRB: 15744
• 分子名称: Apolipoprotein E (1 entity in total)
• 機能のキーワード: apolipoprotein e, lipid transport, atherosclerosis, alzheimer's disease
• 由来する生物種: Homo sapiens (human)
• 細胞内の位置: Secreted: P02649
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 35301.65

構造登録者

Chen, J.,Wang, J. (登録日: 2010-12-07, 公開日: 2011-08-03, 最終更新日: 2024-05-01)

主引用文献

Chen, J.,Li, Q.,Wang, J.
Topology of human apolipoprotein E3 uniquely regulates its diverse biological functions.
Proc.Natl.Acad.Sci.USA, 108:14813-14818, 2011

PubMed Abstract: Human apolipoprotein E (apoE) is one of the major determinants in lipid transport, playing a critical role in atherosclerosis and other diseases. Binding to lipid and heparan sulfate proteoglycans (HSPG) induces apoE to adopt active conformations for binding to low-density lipoprotein receptor (LDLR) family. ApoE also interacts with beta amyloid peptide, manifests critical isoform-specific effects on Alzheimer's disease. Despite the importance of apoE in these major human diseases, the fundamental questions of how apoE adjusts its structure upon binding to regulate its diverse functions remain unsolved. We report the NMR structure of apoE3, displaying a unique topology of three structural domains. The C-terminal domain presents a large exposed hydrophobic surface that likely initiates interactions with lipids, HSPG, and beta amyloid peptides. The unique topology precisely regulates apoE tertiary structure to permit only one possible conformational adaptation upon binding and provides a double security in preventing lipid-free and partially-lipidated apoE from premature binding to apoE receptors during receptor biogenesis. This topology further ensures the optimal receptor-binding activity by the fully lipidated apoE during lipoprotein transport in circulation and in the brain. These findings provide a structural framework for understanding the structural basis of the diverse functions of this important protein in human diseases.

PubMed: 21873229
DOI: 10.1073/pnas.1106420108

実験手法

SOLUTION NMR