Dimeric structure of transmembrane domain of amyloid precursor protein in micellar environment

详细信息	查看全文 | 推荐本文 |

• 作者：Kirill D. Nadezhdin ; Olga V. Bocharova ; Eduard V. Bocharov ; ^bon@nmr.ru ; Alexander S. Arseniev
• 关键词：AD ; Alzheimer&rsquo ; s disease ; APP ; amyloid precursor protein ; A尾 ; amyloid 尾-peptide ; TM ; transmembrane ; JM ; juxtamembrane ; APPjmtm ; APP686&ndash ; 726 fragment ; DPC ; dodecylphosphocholine ; NOE ; nuclear overhauser effect ; NOESY ; NOE spectroscopy ; HSQC ; he
• 出版年：2012
• 期刊代码：70_00145793
• 类别：bio
• 出版时间：12 June, 2012
• 卷：586
• 期：12
• 页码：1687-1692
• 文件大小：988 K

摘要

Some pathogenic mutations associated with Alzheimer鈥檚 disease are thought to affect structural-dynamic properties and the lateral dimerization of amyloid precursor protein (APP) in neuron membrane. Dimeric structure of APP transmembrane fragment Gln⁶⁸⁶-Lys⁷²⁶ was determined in membrane-mimicking dodecylphosphocholine micelles using high-resolution NMR spectroscopy. The APP membrane-spanning 伪-helix Lys⁶⁹⁹-Lys⁷²⁴ self-associates in a left-handed parallel dimer through extended heptad repeat motif I⁷⁰²X₃M⁷⁰⁶X₂G⁷⁰⁹X₃A⁷¹³X₂I⁷¹⁶X₃I⁷²⁰X₂I⁷²³, whereas the juxtamembrane region Gln⁶⁸⁶-Val⁶⁹⁵ constitutes the nascent helix, also sensing the dimerization. The dimerization mechanism of APP transmembrane domain has been described at atomic resolution for the first time and is important for understanding molecular events of APP sequential proteolytical cleavage resulting in amyloid-尾 peptide.

Structured summary of protein interactions

and by ()

and by ().