National Institutes of Health/National Institute on Aging (NIH/NIA)
T32AG058518
米国
National Institutes of Health/National Institute on Aging (NIH/NIA)
RF1NS090934
米国
National Institutes of Health/National Institute on Aging (NIH/NIA)
1U19AG069701
米国
National Science Foundation (NSF, United States)
DGE-1745038
米国
Other private
米国
引用
ジャーナル: Neuron / 年: 2024 タイトル: Apolipoprotein E secreted by astrocytes forms antiparallel dimers in discoidal lipoproteins. 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 ...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 / 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.