Structural Polymorphism of 441-Residue Tau at Single Residue Resolution

• DOI: 10.1371/journal.pbio.1000034
• Publication Date: 2009-02-12T17:22:13Z
• Authors: Marco D Mukrasch; Stefan Bibow; Jegannath Korukottu; Sadasivam Jeganathan; Jacek Biernat; Christian Griesinger; Eckhard Mandelkow; Markus Zweckstetter
• Keywords: Tau protein; Residue (chemistry)

Alzheimer disease is characterized by abnormal protein deposits in the brain, such as extracellular amyloid plaques and intracellular neurofibrillary tangles. The tangles are made of a called tau comprising 441 residues its longest isoform. Tau belongs to class natively unfolded proteins, binds stabilizes microtubules, partially folds into an ordered β-structure during aggregation paired helical filaments (PHFs). Here we show that it possible overcome size limitations have traditionally hampered detailed nuclear magnetic resonance (NMR) spectroscopy studies large nonglobular proteins. This achieved using optimal NMR pulse sequences matching chemical shifts from smaller segments divide conquer strategy. methodology reveals 441-residue highly dynamic solution with distinct domain character intricate network transient long-range contacts important for pathogenic aggregation. Moreover, single-residue view provided analysis unique insights interaction microtubules. Our results establish can provide insight structural polymorphism very