PHF6 Polyclonal Antibody
- Known as:
- PHF6 Polyclonal Antibody
- Catalog number:
- a-2743-50
- Product Quantity:
- USD
- Category:
- -
- Supplier:
- Epigentek inc
- Gene target:
- PHF6 Polyclonal Antibody
Related genes to: PHF6 Polyclonal Antibody
- Gene:
- PHF6 NIH gene
- Name:
- PHD finger protein 6
- Previous symbol:
- BFLS, BORJ
- Synonyms:
- KIAA1823, MGC14797, CENP-31
- Chromosome:
- Xq26.2
- Locus Type:
- gene with protein product
- Date approved:
- 2002-02-28
- Date modifiied:
- 2019-04-23
Related products to: PHF6 Polyclonal Antibody
Related articles to: PHF6 Polyclonal Antibody
- Neurofibrillary tangles, composed of aggregated Tau proteins, are a pathological hallmark of Alzheimer's disease (AD). Within these tangles, the amyloid core is primarily formed by the microtubule-binding (MTB) repeats. Although site-specific acetylation has been implicated in the regulation of Tau aggregation, the atomic-level mechanisms by which individual acetylation events modulate the structure and interactions of amyloid-forming motifs remain incompletely understood. In particular, whether dual acetylation events may act cooperatively during early Tau assembly is still unclear. In this study, we used microsecond-scale all-atom molecular dynamics simulations to systematically examine the dimerization dynamics of the four Tau MTB repeat homodimers (R1-R4). Our simulations suggest that the relatively higher aggregation propensity of R3 and R4 may be associated with amyloidogenic, β-sheet-prone core sequences, in which the key lysine residues K311 and K353 are located. Further analysis indicates that acetylation at these sites attenuates early Tau dimerization: K353 acetylation appears to moderately destabilize the R4 dimer through steric effects and the disruption of intrachain salt bridges, resulting in a more disordered conformational ensemble. K311 acetylation shows a more pronounced inhibitory effect on R3 dimerization by neutralizing the positive charge of K311 and weakening key interchain salt bridges and π-cation interactions associated with the PHF6 motif. Notably, dual acetylation of K311 and K353 in the R3-R4 dimer produces a stronger-than-additive reduction in β-sheet formation. This potential synergistic effect arises from the combined disruption of the hydrophobic core and distal electrostatic interaction networks. In summary, our results provide a molecular-level explanation for how acetylation at K311 and K353 cooperatively modulates Tau dimerization and early amyloid nucleation, offering mechanistic insight into the role of lysine acetylation in Tau aggregation. - Source: PubMed
Publication date: 2026/06/20
Wu JiaxuanHe XinyuFu MinghuaLiu YueSu WanLi RuopengXu MingmingChan Kevin ChunHuang DaiyunWu Sijin - Characterizing the conformational landscapes of intrinsically disordered proteins is essential for elucidating their roles in health and disease, but remains challenging due to their structural heterogeneity. In this study, we introduce an enhanced algorithmic framework for the Energy Landscape Visualization Method (ELViM) that enables the simultaneous mapping of monomeric and oligomeric conformational spaces within a unified metric space. Unlike traditional reaction-coordinate-based approaches, this extended ELViM implementation employs a distance-based similarity metric and force projection embedding to generate low-dimensional representations that preserve high-dimensional structural relationships without predefined bias. We expanded the standard workflow by integrating a density-guided Local Conformational Signature analysis coupled with a new consensus interchain contact mapping protocol. This development allows for the systematic disentanglement of intrachain folding dynamics from the interchain assembly interactions that drive protein aggregation. Using replica exchange molecular dynamics data for a 19-residue fragment of the tau protein, we demonstrate the method's utility by comparing the conformational landscapes of the wild type and the aggregation-associated P301L mutant. ELViM effectively captures continuous conformational transitions and highlights key structural motifs, including the aggregation-prone PHF6 segment (VQIVYK). The analysis reveals how the P301L mutation acts as a structural stabilizer, shifting conformational preferences toward compact, preorganized ensembles with more persistent interchain contacts around PHF6. By providing a quantitative yet intuitive framework for exploring heterogeneous ensembles, this enhanced ELViM workflow offers broad applicability to studying folding landscapes, protein-protein interactions, and complex aggregation pathways. - Source: PubMed
Publication date: 2026/06/18
Sanches Murilo NGanguly PritamShea Joan-EmmaLeite Vitor B P - Pathogenic microtubule-associated protein tau (MAPT) mutations play an important role in tauopathies by altering tau assembly and early aggregation. The V337M mutation, located within the aggregation-prone PHF6** motif of tau, is known to accelerate tau assembly, while its molecular mechanism is unclear. Here, we employ multiscale molecular dynamics simulations, combining replica-exchange, conventional and coarse-grained approaches, to elucidate how the V337M mutation reshapes the conformational ensemble and aggregation behavior of PHF6** peptides. Replica-exchange molecular dynamics simulations demonstrate that the V337M mutation enhances the β-structure and shifts PHF6** oligomers toward more compact aggregates. Interaction analyses show that the V337M mutation facilitates the formation of hydrogen bonds and salt-bridges and strengthens the residue-residue association, with the most pronounced enhancements involving residue 337 and its neighboring residues. Conventional molecular dynamics simulations reveal that the V337M mutation promotes persistent oligomerization and stabilizes β-sheet assemblies in larger PHF6** systems. Coarse-grained simulations establish that β-structure formation is a prerequisite for PHF6** oligomerization and the V337M mutation stabilizes interpeptide association, leading to earlier oligomer formation and more extensively interconnected oligomers. This study provides mechanistic insights into mutation-enhanced tau oligomerization, which may be helpful for an in-depth understanding of the pathogenesis of mutation-linked tauopathies. - Source: PubMed
Publication date: 2026/05/29
Xia PengxuanChen YujieTang JiaxingGuan LuluFeng DushuoZou Yu - Tauopathies are neurodegenerative diseases all characterized by tau lesions in the brain. Nevertheless, a clinical and pathophysiological heterogeneity is present among them. This includes the dominant tau isoform found within aggregates (3R and/or 4R tau) along with different brain regions being affected. For some tauopathies, especially in Alzheimer's disease, a specific spatio-temporal staging of tau lesions is present. This staging has been the basis for the prion-like propagation hypothesis, which describes a cell-to-cell transfer of pathological tau species resulting in new aggregates formation in recipient neurons. Human extracellular vesicles isolated from the brain-derived fluid (BD-EVs) of Alzheimer's disease patients contain seeds that contribute to this tau pathology spreading. However, the nature of these tau species responsible for this nucleation activity remains unknown. Additionally, heterogeneity in seeding activity of BD-EVs of Alzheimer's disease, progressive supranuclear palsy and Pick's disease patients is known. - Source: PubMed
Publication date: 2026/06/15
Oosterlynck MarieFichter LauraLeroux ElodieEddarkaoui SabihaBouillet ThomasLefebvre CamilleNguyen MarineMaurage Claude-AlainAccart BertrandDupré ElianLandrieu IsabelleDanis ClémentLehmann SylvainVialaret JérômeBuée LucHirtz ChristopheColin Morvane - To explore the status of peripheral blood immunological markers and gene mutations in patients with myelodysplastic syndrome (MDS) and the correlation between them. - Source: PubMed
Sun Da-XiangMa YunHan Qiu-HongChen ZhuoLiu Wei-YiWang De-XiuLi Rui-BaiLyu YanXiao Hai-YanLiu ChiLi LiuTang Xu-Dong