2llm Citations

Structural and dynamic study of the transmembrane domain of the amyloid precursor protein.

OpenAccess logo Acta Naturae 3 69-76 (2011)
Cited: 32 times
EuropePMC logo PMID: 22649674

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.

Reviews - 2llm mentioned but not cited (3)

  1. Insights into the physiological function of the β-amyloid precursor protein: beyond Alzheimer's disease. Dawkins E, Small DH. J Neurochem 129 756-769 (2014)
  2. Alzheimer's disease--a panorama glimpse. Zhao LN, Lu L, Chew LY, Mu Y. Int J Mol Sci 15 12631-12650 (2014)
  3. The Role of Proteolysis in Amyloidosis. Acquasaliente L, De Filippis V. Int J Mol Sci 24 699 (2022)

Articles - 2llm mentioned but not cited (11)



Reviews citing this publication (5)

  1. Understanding single-pass transmembrane receptor signaling from a structural viewpoint-what are we missing? Bugge K, Lindorff-Larsen K, Kragelund BB. FEBS J 283 4424-4451 (2016)
  2. Regulation of the alternative β-secretase meprin β by ADAM-mediated shedding. Scharfenberg F, Armbrust F, Marengo L, Pietrzik C, Becker-Pauly C. Cell Mol Life Sci 76 3193-3206 (2019)
  3. Structural Studies Providing Insights into Production and Conformational Behavior of Amyloid-β Peptide Associated with Alzheimer's Disease Development. Urban AS, Pavlov KV, Kamynina AV, Okhrimenko IS, Arseniev AS, Bocharov EV. Molecules 26 2897 (2021)
  4. Deuterated detergents for structural and functional studies of membrane proteins: Properties, chemical synthesis and applications. Hiruma-Shimizu K, Shimizu H, Thompson GS, Kalverda AP, Patching SG. Mol Membr Biol 32 139-155 (2015)
  5. Role of Mitochondrial Protein Import in Age-Related Neurodegenerative and Cardiovascular Diseases. Bogorodskiy A, Okhrimenko I, Burkatovskii D, Jakobs P, Maslov I, Gordeliy V, Dencher NA, Gensch T, Voos W, Altschmied J, Haendeler J, Borshchevskiy V. Cells 10 3528 (2021)

Articles citing this publication (13)