2LLM

Structure of amyloid precursor protein's transmembrane domain

2LLM の概要

• エントリーDOI: 10.2210/pdb2llm/pdb
• NMR情報: BMRB: 18080
• 分子名称: Amyloid beta A4 protein (1 entity in total)
• 機能のキーワード: alzheimer's disease, protein fibril
• 由来する生物種: Homo sapiens (human)
• 細胞内の位置: Membrane; Single-pass type I membrane protein: P05067
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 4450.46

構造登録者

Nadezhdin, K.D.,Bocharova, O.V.,Bocharov, E.V.,Arseniev, A.S. (登録日: 2011-11-15, 公開日: 2012-06-20, 最終更新日: 2024-05-15)

主引用文献

Nadezhdin, K.D.,Bocharova, O.V.,Bocharov, E.V.,Arseniev, A.S.
Structural and dynamic study of the transmembrane domain of the amyloid precursor protein.
Acta Naturae, 3:69-76, 2011

PubMed Abstract: Alzheimer's disease affects people all over the world, regardless of nationality, gender or social status. An adequate study of the disease requires essential understanding of the molecular fundamentals of the pathogenesis. The amyloid β-peptide, which forms amyloid plaques in the brain of people with Alzheimer's disease, is the product of sequential cleavage of a single-span membrane amyloid precursor protein (APP). More than half of the APP mutations found to be associated with familial forms of Alzheimer's disease are located in its transmembrane domain. The pathogenic mutations presumably affect the structural-dynamic properties of the APP transmembrane domain by changing its conformational stability and/or lateral dimerization. In the present study, the structure and dynamics of the recombinant peptide corresponding to the APP fragment, Gln686-Lys726, which comprises the APP transmembrane domain with an adjacent N-terminal juxtamembrane sequence, were determined in the membrane mimetic environment composed of detergent micelles using NMR spectroscopy. The structure obtained in dodecylphosphocholine micelles consists of two α-helices: a short surface-associated juxtamembrane helix (Lys687-Asp694) and a long transmembrane helix (Gly700-Leu723), both connected via a mobile loop region. A minor bend of the transmembrane α-helix is observed near the paired residues Gly708-Gly709. A cholesterol-binding hydrophobic cavity is apparently formed under the loop region, where the juxtamembrane α-helix comes into contact with the membrane surface near the N-terminus of the transmembrane α-helix.

PubMed: 22649674

実験手法

SOLUTION NMR