Home News About Us Contact Contributors Disclaimer Privacy Policy Help FAQ

Home
Search
Quick Search
Advanced
Fulltext
Browse
Collections
Persons
My eDoc
Session History
Login
Name:
Password:
Documentation
Help
Support Wiki
Direct access to
document ID:


          Institute: Max-Planck-Arbeitsgruppen für strukturelle Molekularbiologie     Collection: Arbeitsgruppe Zytoskelett     Display Documents



  history
ID: 333627.0, Max-Planck-Arbeitsgruppen für strukturelle Molekularbiologie / Arbeitsgruppe Zytoskelett
The "jaws" of the tau-microtubule interaction
Authors:Mukrasch, M. D.; von Bergen, M.; Biernat, J.; Fischer, D.; Griesinger, C.; Mandelkow, E.; Zweckstetter, M.
Language:English
Date of Publication (YYYY-MM-DD):2007-04-20
Title of Journal:Journal of Biological Chemistry
Journal Abbrev.:J Biol Chem
Volume:282
Issue / Number:16
Start Page:12230
End Page:12239
Review Status:not specified
Audience:Not Specified
Abstract / Description:Tau is the major microtubule-associated protein in neuronal axons. It aggregates into "neurofibrillary tangles" during the course of Alzheimer disease. Binding to microtubules and microtubule assembly requires the "repeat domain" in the C-terminal half of Tau, as well as the two regions flanking the repeats. Here we report the NMR characterization of a 198-residue Tau fragment composed of the four tandem repeats and the flanking domains and containing the full microtubule binding and assembly activity of Tau. NMR secondary chemical shifts and dipolar couplings detect the highest propensity for beta-structure within the four-repeat region, whereas the flanking domains are largely random coil, with an increased rigidity in the proline-rich region. Chemical shift perturbation experiments identify two motifs in the upstream flanking domain, (225)KVAVVRT(231) and (243)LQTA(246), and one downstream of the repeats, (370)KIETHKTFREN(380), which strongly contribute to the binding to the acidic outside of microtubules, as well as to the binding of other polyanions such as heparin. This is consistent with the "jaws" model of Tau-microtubule interactions and highlights the importance of the regions flanking the repeats for both microtubule binding and pathological Tau aggregation.
Free Keywords:Alzheimer Disease/metabolism; Amino Acid Sequence; Anions; Humans; Ions; Magnetic Resonance Spectroscopy; Microtubules/chemistry/*metabolism; Models, Chemical; Molecular Sequence Data; Phosphorylation; Protein Binding; Protein Structure, Secondary; Protein Structure, Tertiary; Recombinant Proteins/chemistry; tau Proteins/*chemistry
External Publication Status:published
Document Type:Article
Communicated by:N. N.
Affiliations:Max-Planck-Arbeitsgruppen für strukturelle Molekularbiologie/Zytoskelett
The scope and number of records on eDoc is subject to the collection policies defined by each institute - see "info" button in the collection browse view.