title: Structural memory of natively unfolded tau protein detected by small-angle X-ray scattering.
abstract: Small-angle X-ray scattering (SAXS) is a universal low-resolution method to study size and shape of globular proteins in solution but recent developments facilitate the quantitative characterization of the structure and structural transitions of metastable systems like partially or completely unfolded proteins. We present here a study of temperature induced transitions in tau, a natively unfolded protein involved in Alzheimer's disease. Previous studies on full length tau and several disease-related mutants provided information about the residual structure in different domains revealing a specific role and extended conformations of the so-called repeat domains, which are considered to be responsible for the formation of amyloid-like fibrils ("paired helical filaments"). Here, we employ SAXS to investigate the temperature dependent properties of tau. Slow heating/cooling of the full length protein from 10°C to 50°C did not lead to detectable changes in the overall size. Surprisingly, quick heating/cooling caused tau to adopt a significantly more compact conformation, which was stable over up to 3 h and represents a structural "memory" effect. This compaction is not observed for the shorter tau constructs containing largely the repeat domains. The structural and functional implications of the observed unusual behavior of tau under nonequilibrium conditions are discussed.
authors.affiliation: European Molecular Biology Laboratory, Hamburg Outstation c/o DESY, Notkestrasse 85, 22603 Hamburg, Germany.
authors.forename: Alexander V
authors.initials: AV
authors.lastname: Shkumatov
authors.forename: Subashchandrabose
authors.initials: S
authors.lastname: Chinnathambi
authors.forename: Eckhard
authors.initials: E
authors.lastname: Mandelkow
authors.forename: Dmitri I
authors.initials: DI
authors.lastname: Svergun
mesh_terms: D002942:Circular Dichroism; D006801:Humans; D011487:Protein Conformation; D020033:Protein Isoforms; D058767:Protein Unfolding; D053838:Scattering, Small Angle; D013696:Temperature; D014961:X-Ray Diffraction; D016875:tau Proteins / Q000737:chemistry* / Q000378:metabolism
chemical_list: D020033:Protein Isoforms; D016875:tau Proteins