Unraveling the Molecular Dance: Insights into TREM2/DAP12 Complex Formation in Alzheimer's Disease through Molecular Dynamics Simulations.

ABSTRACT: Alzheimer's disease (AD) is a widespread neurodegenerative condition affecting millions globally. Recent research has implicated variants of the triggering receptor expressed in myeloid cells 2 (TREM2) as risk factors for AD. TREM2, an immunomodulatory receptor on microglial surfaces, plays a pivotal role in regulating microglial activation by association with DNAX-activation protein 12 (DAP12). Despite its significance, the mechanism underlying the formation of the complex between the transmembrane domains (TMDs) of TREM2 and DAP12 remains unclear. This study employs multiscale molecular dynamics (MD) simulations to investigate three TMD complex models, including two derived from experiments and one generated by AlphaFold2. Conducted within a lipid membrane consisting of an 80:20 mixture

SUBMITTER: Zhong Z 

PROVIDER: S-EPMC11223195 | biostudies-literature | 2024 Jul

REPOSITORIES: biostudies-literature