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15N-Tau-441, Uniformly Labeled, Human, Recombinant

Sequence: MGSSHHHHHHSSG MAEPRQEFEV MEDHAGTYGL GDRKDQGGYT MHQDQEGDTD AGLKESPLQT PTEDGSEEPG SETSDAKSTP TAEDVTAPLV DEGAPGKQAA AQPHTEIPEG TTAEEAGIGD TPSLEDEAAG HVTQARMVSK SKDGTGSDDK KAKGADGKTK IATPRGAAPP GQKGQANATR IPAKTPPAPK TPPSSGEPPK SGDRSGYSSP GSPGTPGSRS RTPSLPTPPT REPKKVAVVR TPPKSPSSAK SRLQTAPVPM PDLKNVKSKI GSTENLKHQP GGGKVQIINK KLDLSNVQSK CGSKDNIKHV PGGGSVQIVY KPVDLSKVTS KCGSLGNIHH KPGGGQVEVK SEKLDFKDRV QSKIGSLDNI THVPGGGNKK IETHKLTFRE NAKAKTDHGA EIVYKSPVVS GDTSPRHLSN VSSTGSIDMV DSPQLATLAD EVSASLAKQG L (N-terminal His-Tag)

           
Product Catalog # SizePrice (USD) Quantity
$400.00
$600.00
$2,400.00
Synonym: 15N Stable Isotope Labeled -Tau-441; 15N-FTDP-17; 15N-TAU; 15N-MAPT; 15N-Microtubule Associated Protein Tau
UniProt ID: P10636-8
Source: E. coli
Molecular Formula: C2016H3274(15N)606O686S9
Molecular Weight: 47872.4
Uniformly 15N isotope-labeled Tau-441 is a powerful stable isotope-labeled protein reagent widely used in Alzheimer’s disease and neurodegenerative disease research. Tau-441 (also known as the full-length human Tau isoform containing 441 amino acids) is the longest major CNS tau isoform and plays a central role in the formation of pathological neurofibrillary tangles through abnormal aggregation and hyperphosphorylation. Incorporation of 15N throughout the protein enables advanced multidimensional nuclear magnetic resonance (NMR) spectroscopy, allowing researchers to investigate tau conformational dynamics, aggregation mechanisms, protein interactions, and therapeutic strategies. Due to tau’s intrinsically disordered nature and complex aggregation behavior, uniformly 15N-labeled Tau-441 serves as an essential tool for structural biology and drug discovery studies.
1. Introduction
Tau is a microtubule-associated protein primarily responsible for stabilizing neuronal microtubules. In the human brain, alternative splicing of the MAPT gene generates six major tau isoforms ranging from 352 to 441 amino acids. Among these, Tau-441 (2N4R tau) contains two N-terminal inserts and four microtubule-binding repeats and represents the longest adult human tau isoform.
In Alzheimer’s disease (AD) and other tauopathies, tau undergoes abnormal post-translational modifications, including hyperphosphorylation, misfolding, and aggregation into paired helical filaments (PHFs) and neurofibrillary tangles (NFTs). Understanding tau aggregation pathways is therefore critical for elucidating disease mechanisms and developing anti-tau therapeutics.
2. Importance of 15N Isotope Labeling
Uniform labeling of Tau-441 with 15N provides significant advantages for structural and biochemical studies:
• Enables high-resolution 1H-15N HSQC NMR spectroscopy.
• Allows residue-specific monitoring of tau conformational changes.
• Facilitates backbone resonance assignments of this highly flexible protein.
• Enables investigation of transient aggregation intermediates.
• Supports interaction studies with ligands, antibodies, microtubules, and regulatory proteins.
• Provides enhanced sensitivity for monitoring phosphorylation-induced or ligand-induced structural changes.
Because 15N is a stable, non-radioactive isotope, isotope incorporation does not significantly alter tau’s native biological properties.
3. Structural Characteristics of Tau-441
Tau-441 is an intrinsically disordered protein (IDP) with highly dynamic conformational behavior. Unlike globular proteins, tau does not adopt a single stable three-dimensional structure under physiological conditions.
Major functional regions include:
N-Terminal Projection Domain
• Regulates interactions with cellular partners.
• Influences microtubule organization and signaling pathways.
Proline-Rich Region
• Contains multiple phosphorylation sites.
• Participates in interactions with SH3-domain-containing proteins.
Microtubule-Binding Repeat Domain (R1–R4)
• Responsible for binding and stabilizing microtubules.
• Contains aggregation-prone sequences involved in fibril formation.
C-Terminal Region
• Modulates tau interactions and aggregation behavior.
The repeat domain, particularly the hexapeptide motifs VQIVYK (residues 275-280) and VQIINK (residues 306-311), plays a key role in tau self-assembly into amyloid fibrils.
4. Major Research Applications
4.1 Tau Aggregation Studies
Uniformly 15N-labeled Tau-441 enables researchers to monitor:
• Early conformational transitions
• Liquid–liquid phase separation (LLPS)
• Oligomer formation
• Fibril nucleation and elongation
• Effects of aggregation-promoting factors such as heparin and RNA
NMR studies provide residue-level information about regions involved in tau misfolding and aggregation.
4.2 Protein NMR and Structural Biology
15N Tau-441 is widely used for:
• Backbone resonance assignment
• Chemical shift perturbation analysis
• Relaxation and dynamics measurements
• Mapping molecular interactions
• Studying tau conformational ensembles
These approaches are particularly valuable because tau’s intrinsically disordered nature limits conventional structural techniques.
4.3 Tau-Ligand and Drug Discovery Studies
The labeled protein supports screening and characterization of:
• Small-molecule tau aggregation inhibitors
• Anti-tau antibodies
• Peptide-based inhibitors
• Molecular chaperone interactions
• Tau-targeting therapeutic candidates
Residue-specific NMR analysis allows researchers to identify binding regions and mechanisms of action.
4.4 Studies of Tau Post-Translational Modifications
Tau pathology is strongly influenced by modifications such as:
• Phosphorylation
• Acetylation
• Ubiquitination
• Glycosylation
Uniformly 15N-labeled Tau-441 provides a platform for studying how these modifications regulate protein structure, dynamics, and aggregation.
5. Future Perspectives
Uniformly 15N-labeled Tau-441 will continue to contribute to advances in tau biology, including:
• High-resolution mapping of tau aggregation pathways
• Structural studies combining NMR and cryo-EM
• Mechanistic studies of tau spreading between neurons
• Development of next-generation anti-tau therapeutics
• Investigation of tau phase separation and biomolecular condensates
Uniformly 15N isotope-labeled Tau-441 is an essential research reagent for studying tau structure, dynamics, aggregation, and pathological mechanisms associated with Alzheimer’s disease and other tauopathies. By enabling residue-specific analysis through advanced NMR techniques, 15N Tau-441 provides unique insights into the molecular events underlying neurodegeneration and supports the discovery of novel tau-targeted therapeutic approaches.

For Research & Development use only. Not for testing and/or use on humans.

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