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Tau Protein pp 89-100 | Cite as

X-Ray Structural Study of Amyloid-Like Fibrils of Tau Peptides Bound to Small-Molecule Ligands

  • Einav Tayeb-Fligelman
  • Meytal Landau
Protocol
Part of the Methods in Molecular Biology book series (MIMB, volume 1523)

Abstract

Atomic structures of Tau involved in Alzheimer’s disease complexed with small molecule binders are the first step to define the Tau pharmacophore, leading the way to a structure-based design of improved diagnostics and therapeutics. Yet the partially disordered and polymorphic nature of Tau hinders structural analyses. Fortunately, short segments from amyloid proteins, which exhibit similar biophysical properties to the full-length proteins, also form fibrils and oligomers, and their atomic structures can be determined using X-ray microcrystallography. Such structures were successfully used to design amyloid inhibitors. This chapter describes experimental procedures used to determine crystal structures of Tau peptide segments in complex with small-molecule binders.

Key words

Tau Alzheimer’s disease Small molecules Pharmacophore Microcrystals Amyloid-like peptides Microcrystallography 

Notes

Acknowledgments

ML thanks the U.S.-Israel Binational Science Foundation (BSF), Alon Fellowship from the Israeli Council for Higher Education, David and Inez Mayers Career Advancement Chair in Life Sciences, the J. and A. Tau Biological Research Fund, the I-CORE Program of the Planning and Budgeting Committee and The Israel Science Foundation, Center of Excellence in Integrated Structural Cell Biology; Grant No 1775/12, and the Support for training and career development of researchers (Marie Curie) CIG, Seventh framework program, Single Beneficiary.

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Copyright information

© Springer Science+Business Media New York 2017

Authors and Affiliations

  1. 1.Department of BiologyTechnion-Israel Institute of TechnologyHaifaIsrael

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