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-Structure paper
タイトル | Apolipoprotein E secreted by astrocytes forms antiparallel dimers in discoidal lipoproteins. |
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ジャーナル・号・ページ | Neuron, Vol. 112, Issue 7, Page 1100-11109.e5, Year 2024 |
掲載日 | 2024年4月3日 |
著者 | Michael R Strickland / Michael J Rau / Brock Summers / Katherine Basore / John Wulf / Hong Jiang / Yun Chen / Jason D Ulrich / Gwendalyn J Randolph / Rui Zhang / James A J Fitzpatrick / Anil G Cashikar / David M Holtzman / |
PubMed 要旨 | The Apolipoprotein E gene (APOE) is of great interest due to its role as a risk factor for late-onset Alzheimer's disease. ApoE is secreted by astrocytes in the central nervous system in high-density ...The Apolipoprotein E gene (APOE) is of great interest due to its role as a risk factor for late-onset Alzheimer's disease. ApoE is secreted by astrocytes in the central nervous system in high-density lipoprotein (HDL)-like lipoproteins. Structural models of lipidated ApoE of high resolution could aid in a mechanistic understanding of how ApoE functions in health and disease. Using monoclonal Fab and F(ab') fragments, we characterize the structure of lipidated ApoE on astrocyte-secreted lipoproteins. Our results provide support for the "double-belt" model of ApoE in nascent discoidal HDL-like lipoproteins, where two ApoE proteins wrap around the nanodisc in an antiparallel conformation. We further show that lipidated, recombinant ApoE accurately models astrocyte-secreted ApoE lipoproteins. Cryogenic electron microscopy of recombinant lipidated ApoE further supports ApoE adopting antiparallel dimers in nascent discoidal lipoproteins. |
リンク | Neuron / PubMed:38266643 / PubMed Central |
手法 | EM (単粒子) |
解像度 | 7.71 - 8.73 Å |
構造データ | EMDB-41830: Lipidated recombinant apolipoprotein E4 EMDB-41831: Gradient-fixed lipidated recombinant apolipoprotein E4 |
由来 |
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