The tau protein is found predominantly in the neurons of the central nervous system, where it helps maintain the internal structure of nerve cells. A protein’s molecular weight, which refers to its mass, is a fundamental characteristic providing insights into its physical properties.
Understanding Molecular Weight in Proteins
Molecular weight represents the mass of a molecule, typically measured in Daltons (Da) or kilodaltons (kDa). For proteins, it is directly influenced by the number and types of amino acids that compose the protein chain. This measurement is significant because it influences a protein’s overall size, three-dimensional shape, and its ability to interact with other molecules within the cell. It helps researchers understand how a protein folds, where it is located, and what other cellular components it might bind to.
The Tau Protein: Structure, Isoforms, and Molecular Weight
The tau protein stabilizes microtubules, which are structural components within neurons that act like tracks for transporting materials. Tau binds directly to tubulin, the building block of microtubules, promoting their assembly and stability.
Tau exists in multiple forms called isoforms, generated from the MAPT gene on chromosome 17 through alternative splicing. The adult human brain contains six main tau isoforms, ranging from 352 to 441 amino acids. These isoforms differ in their amino acid sequences due to the inclusion or exclusion of segments encoded by exons 2, 3, and 10. This results in a range of molecular weights for human tau, typically between 48 kDa and 68 kDa when observed on SDS gels, though the true molecular weight is between 37 and 46 kDa.
Some isoforms are categorized by their microtubule-binding repeats (3R or 4R tau), affecting their binding affinity. A larger isoform, “Big tau,” around 110 kDa, is mainly expressed in the peripheral nervous system and contains an additional large exon.
Tau’s Molecular Weight in Health and Disease
In neurodegenerative diseases known as tauopathies, including Alzheimer’s disease, tau undergoes significant alterations, particularly hyperphosphorylation. This means an excessive number of phosphate groups attach to the tau protein, often at more than 40 sites, significantly higher than in normal brain tissue. This hyperphosphorylation reduces tau’s ability to bind to and stabilize microtubules, leading to their destabilization.
Hyperphosphorylated tau then detaches from microtubules, misfolds, and aggregates, forming insoluble clumps within neurons. These aggregates include tau oligomers (small clusters of tau proteins) and neurofibrillary tangles (NFTs), a hallmark of Alzheimer’s disease and other tauopathies. While the actual molecular weight of the tau protein itself doesn’t change, the addition of phosphate groups and aggregate formation cause an increase in its apparent molecular weight when analyzed using laboratory techniques like SDS-PAGE. For instance, hyperphosphorylated tau extracted from Alzheimer’s disease brains can show an apparent molecular weight of 67-70 kDa. The presence of these higher apparent molecular weight forms, particularly hyperphosphorylated tau oligomers, is considered more relevant than a static molecular weight, as they indicate the protein’s modified state and its propensity to aggregate, contributing to neuronal dysfunction and loss in these diseases.