Translational Neuroscience (Apr 2022)

Molecular recognition of the interaction between ApoE and the TREM2 protein

  • Mai Zhenhua,
  • Wei Wenyan,
  • Yu Haibin,
  • Chen Yongze,
  • Wang Yongxiang,
  • Ding Yuanlin

DOI
https://doi.org/10.1515/tnsci-2022-0218
Journal volume & issue
Vol. 13, no. 1
pp. 93 – 103

Abstract

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Alzheimer’s disease (AD) is the most common type of dementia. The ε4 allele of the apolipoprotein E (ApoE) gene is the strongest known genetic risk factor for late-onset AD. Triggering receptor expressed on myeloid cells 2 (TREM2) is another important risk factor affecting the AD process after ApoE. Emerging evidence has identified TREM2 as a putative receptor for ApoE, raising the possibility that interactions between ApoE and TREM2 modulate the pathogenesis of AD. In this study, we performed molecular docking and molecular dynamics (MD) analyses to characterize the ApoE–TREM2 interaction and further investigated the effect of the major TREM2 disease-associated mutation (R47H) on the affinity of TREM2 for ApoE. The results indicate that the binding energy between ApoE and TREM2 occurs in an isoform-dependent manner with the following potency rank order: ApoE4 > ApoE3 > ApoE2. In addition, the R47H mutant reduced the interaction between ApoE and TREM2 protein, which may be attributed to decreased hydrogen-bonding interactions, hydrophobic interactions, and electrostatic forces between ApoE and TREM2. Our study analyzed the molecular pattern of the interactions between ApoE and TREM2 and how the variants affect these interactions based on in silico modeling, and the results might help to elucidate the interaction mechanism between ApoE and TREM2. Additional experimental studies will be needed to verify and explore the current findings.

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