Microtubule-associated protein tau (MAPT) microtubule-binding region HVPGG motif (Tau MTBR HVPGG)

The microtubule-associated protein tau (MAPT) is a critical component of the neuronal cytoskeleton, primarily responsible for stabilizing microtubules in axons (UniProt: P10636). The microtubule-binding region (MTBR) of tau contains three or four highly conserved repeats, each ending with a characteristic HVPGG motif or its variants. This motif plays a dual role: it facilitates the binding of tau to microtubules under physiological conditions and serves as a nucleation site for the formation of pathological tau aggregates in neurodegenerative diseases (von Bergen et al., 2000). In tauopathies such as Alzheimer's disease, the HVPGG motif undergoes conformational changes that promote the assembly of tau into paired helical filaments (PHFs) and neurofibrillary tangles (Wischik et al., 2014). Therapeutic strategies targeting this motif aim to inhibit the aggregation process or promote the disassembly of existing aggregates. Small molecules like hydromethylthionine mesylate (LMTM) have been designed to interact with the MTBR to prevent the pathological transition of tau (Gerson et al., 2014). Understanding the structural dynamics of the HVPGG motif is essential for developing effective disease-modifying treatments for tau-mediated neurodegeneration.

Other names

Tau repeat domain motifTau PGG motifTau microtubule-binding domain motifTau MTBD motifTau MTBR repeat motif

Inhibition of tau-tau interaction and dissolution of paired helical filaments (PHFs) by binding to the repeat domain and preventing beta-sheet formation.