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On the structure of microtubules, tau, and paired helical filaments
E Mandelkow1, Y H Song, O Schweers
1Max-Planck-Unit for Structural Molecular Biology, Hamburg, Germany.
Abstract:
Microtubules and their associated proteins form the basis of axonal transport; they are degraded during the neuronal degeneration in Alzheimer's disease. This article surveys recent results on the structure of microtubules, tau protein, and PHFs. Microtubules have been investigated by electron microscopy and image processing after labeling them with the head domain of the motor protein kinesin. This reveals the arrangement of tubulin subunits in microtubules and the shape of the tubulin-motor complex. Tau protein was studied by electron microscopy, solution X-ray scattering, and spectroscopic methods. It appears as an elongated molecule (about 35 nm) without recognizable secondary structure. Alzheimer PHFs were examined by FTIR and X-ray diffraction; they, too, show evidence for secondary structure such as beta sheets.
Insights
This study investigates the structure of microtubules and tau protein, crucial for axonal transport and affected in Alzheimer's disease. Findings reveal microtubule arrangements and tau protein
Area of Science:
- Neuroscience
- Biochemistry
- Structural Biology
Background:
- Microtubules and associated proteins are vital for axonal transport.
- Neuronal degeneration in Alzheimer's disease involves microtubule breakdown.
- Understanding the structure of microtubules, tau protein, and paired helical filaments (PHFs) is key to Alzheimer's research.
Purpose of the Study:
- To survey recent findings on the structure of microtubules, tau protein, and PHFs.
- To elucidate the structural basis of axonal transport and its disruption in Alzheimer's disease.
Main Methods:
- Microtubule structure was analyzed using electron microscopy and image processing with kinesin motor protein domains.
- Tau protein structure was investigated via electron microscopy, solution X-ray scattering, and spectroscopy.
- Alzheimer's PHFs were examined using Fourier-transform infrared spectroscopy (FTIR) and X-ray diffraction.
Main Results:
- Electron microscopy revealed the arrangement of tubulin subunits in microtubules and the structure of tubulin-kinesin complexes.
- Tau protein was characterized as an elongated molecule (~35 nm) lacking discernible secondary structure.
- FTIR and X-ray diffraction indicated the presence of beta-sheet secondary structures in Alzheimer's PHFs.
Conclusions:
- The study provides structural insights into key components of axonal transport and their alterations in Alzheimer's disease.
- Structural characterization of microtubules, tau, and PHFs contributes to understanding neurodegenerative mechanisms.