Amyloid Precursor Protein Changes Arrangement in a Membrane and Its Structure Depending on the Cholesterol Content
One of the hallmarks of Alzheimer’s disease (AD) is the accumulation of amyloid beta (Aβ) peptides in the brain. The processing of amyloid precursor protein (APP) into Aβ is dependent on the location of APP in the membrane, membrane lipid composition and, possibly, presence of lipid rafts. In this s...
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MDPI AG
2023-07-01
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| Series: | Membranes |
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| Online Access: | https://www.mdpi.com/2077-0375/13/8/706 |
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| author | Vladimir D. Krasnobaev Yaroslav V. Bershatsky Olga V. Bocharova Eduard V. Bocharov Oleg V. Batishchev |
| author_facet | Vladimir D. Krasnobaev Yaroslav V. Bershatsky Olga V. Bocharova Eduard V. Bocharov Oleg V. Batishchev |
| author_sort | Vladimir D. Krasnobaev |
| collection | DOAJ |
| description | One of the hallmarks of Alzheimer’s disease (AD) is the accumulation of amyloid beta (Aβ) peptides in the brain. The processing of amyloid precursor protein (APP) into Aβ is dependent on the location of APP in the membrane, membrane lipid composition and, possibly, presence of lipid rafts. In this study, we used atomic force microscopy (AFM) to investigate the interaction between transmembrane fragment APP<sub>672–726</sub> (corresponding to Aβ<sub>1–55</sub>) and its amyloidogenic mutant L723P with membranes combining liquid-ordered and liquid-disordered lipid phases. Our results demonstrated that most of the APP<sub>672–726</sub> is located either in the liquid-disordered phase or at the boundary between ordered and disordered phases, and hardly ever in rafts. We did not notice any major changes in the domain structure induced by APP<sub>672–726</sub>. In membranes without cholesterol APP<sub>672–726</sub>, and especially its amyloidogenic mutant L723P formed annular structures and clusters rising above the membrane. Presence of cholesterol led to the appearance of concave membrane regions up to 2 nm in depth that were deeper for wild type APP<sub>672–726</sub>. Thus, membrane cholesterol regulates changes in membrane structure and permeability induced by APP that might be connected with further formation of membrane pores. |
| first_indexed | 2024-03-10T23:44:52Z |
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| id | doaj.art-b25979ecf2ab4069820d3e25ad924d01 |
| institution | Directory Open Access Journal |
| issn | 2077-0375 |
| language | English |
| last_indexed | 2024-03-10T23:44:52Z |
| publishDate | 2023-07-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Membranes |
| spelling | doaj.art-b25979ecf2ab4069820d3e25ad924d012023-11-19T02:07:40ZengMDPI AGMembranes2077-03752023-07-0113870610.3390/membranes13080706Amyloid Precursor Protein Changes Arrangement in a Membrane and Its Structure Depending on the Cholesterol ContentVladimir D. Krasnobaev0Yaroslav V. Bershatsky1Olga V. Bocharova2Eduard V. Bocharov3Oleg V. Batishchev4Frumkin Institute of Physical Chemistry and Electrochemistry, Russian Academy of Sciences, Leninsky Prospekt, 31, 119071 Moscow, RussiaResearch Center for Molecular Mechanisms of Aging and Age-related Diseases, Moscow Institute of Physics and Technology, Institutski per., 9, 141701 Dolgoprudny, Moscow Region, RussiaShemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, Miklukho-Maklaya, 16/10, 117997 Moscow, RussiaResearch Center for Molecular Mechanisms of Aging and Age-related Diseases, Moscow Institute of Physics and Technology, Institutski per., 9, 141701 Dolgoprudny, Moscow Region, RussiaFrumkin Institute of Physical Chemistry and Electrochemistry, Russian Academy of Sciences, Leninsky Prospekt, 31, 119071 Moscow, RussiaOne of the hallmarks of Alzheimer’s disease (AD) is the accumulation of amyloid beta (Aβ) peptides in the brain. The processing of amyloid precursor protein (APP) into Aβ is dependent on the location of APP in the membrane, membrane lipid composition and, possibly, presence of lipid rafts. In this study, we used atomic force microscopy (AFM) to investigate the interaction between transmembrane fragment APP<sub>672–726</sub> (corresponding to Aβ<sub>1–55</sub>) and its amyloidogenic mutant L723P with membranes combining liquid-ordered and liquid-disordered lipid phases. Our results demonstrated that most of the APP<sub>672–726</sub> is located either in the liquid-disordered phase or at the boundary between ordered and disordered phases, and hardly ever in rafts. We did not notice any major changes in the domain structure induced by APP<sub>672–726</sub>. In membranes without cholesterol APP<sub>672–726</sub>, and especially its amyloidogenic mutant L723P formed annular structures and clusters rising above the membrane. Presence of cholesterol led to the appearance of concave membrane regions up to 2 nm in depth that were deeper for wild type APP<sub>672–726</sub>. Thus, membrane cholesterol regulates changes in membrane structure and permeability induced by APP that might be connected with further formation of membrane pores.https://www.mdpi.com/2077-0375/13/8/706Alzheimer’s disease (AD)amyloid precursor protein (APP)atomic force microscopy (AFM)amyloidogenic mutant L723Pamyloid beta (Aβ) peptideslipid raft |
| spellingShingle | Vladimir D. Krasnobaev Yaroslav V. Bershatsky Olga V. Bocharova Eduard V. Bocharov Oleg V. Batishchev Amyloid Precursor Protein Changes Arrangement in a Membrane and Its Structure Depending on the Cholesterol Content Membranes Alzheimer’s disease (AD) amyloid precursor protein (APP) atomic force microscopy (AFM) amyloidogenic mutant L723P amyloid beta (Aβ) peptides lipid raft |
| title | Amyloid Precursor Protein Changes Arrangement in a Membrane and Its Structure Depending on the Cholesterol Content |
| title_full | Amyloid Precursor Protein Changes Arrangement in a Membrane and Its Structure Depending on the Cholesterol Content |
| title_fullStr | Amyloid Precursor Protein Changes Arrangement in a Membrane and Its Structure Depending on the Cholesterol Content |
| title_full_unstemmed | Amyloid Precursor Protein Changes Arrangement in a Membrane and Its Structure Depending on the Cholesterol Content |
| title_short | Amyloid Precursor Protein Changes Arrangement in a Membrane and Its Structure Depending on the Cholesterol Content |
| title_sort | amyloid precursor protein changes arrangement in a membrane and its structure depending on the cholesterol content |
| topic | Alzheimer’s disease (AD) amyloid precursor protein (APP) atomic force microscopy (AFM) amyloidogenic mutant L723P amyloid beta (Aβ) peptides lipid raft |
| url | https://www.mdpi.com/2077-0375/13/8/706 |
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