Crystallization and preliminary X-ray diffraction analysis of tau protein microtubule-binding motifs in complex with Tau5 and DC25 antibody Fab fragments

• Published in: Acta crystallographica. Section F, Structural biology and crystallization communications Structural biology and crystallization communications, 2012-10, Vol.68 (10), p.1181-1185
• Main Authors: Cehlar, Ondrej, Skrabana, Rostislav, Kovac, Andrej, Kovacech, Branislav, Novak, Michal
• Format: Article
• Language: English
• Subjects: Amino Acid Motifs; Antibodies, Monoclonal; Crystallization; Crystallization Communications; Crystallography, X-Ray; Crystals; Deposition; Diffraction; Fab fragments; Fragments; Immunoglobulin Fab Fragments - chemistry; Immunoglobulin Fab Fragments - immunology; intrinsically disordered proteins; microtubule binding; Microtubules - chemistry; Microtubules - metabolism; Protein Structure, Tertiary; Proteins; Synchrotrons; tau protein; tau Proteins - chemistry; tau Proteins - immunology; tau Proteins - metabolism; X-ray sources; X-rays
• ISSN: 1744-3091; 1744-3091; 2053-230X
• DOI: 10.1107/S1744309112030382

The Alzheimer's disease‐associated protein tau is an intrinsically disordered protein with no preferred structure in solution. Under physiological conditions, tau binds to microtubules and regulates their dynamics, whereas during the development of neurodegeneration tau dissociates from microtubules, misfolds and creates highly insoluble deposits. To elucidate the determinants of tau‐protein misfolding, tau peptides from microtubule‐binding motifs were crystallized in complexes with Fab fragments of specific monoclonal antibodies. The crystals diffracted to 1.69 Å resolution and gave complete data sets using a synchrotron X‐ray source. Molecular replacement was used to solve the phase problem.