2V17

Structure of the complex of antibody MN423 with a fragment of tau protein

Summary for 2V17

• Entry DOI: 10.2210/pdb2v17/pdb
• Descriptor: PEPTIDE FRAGMENT, MONOCLONAL ANTIBODY FAB FRAGMENT MN423, ... (4 entities in total)
• Functional Keywords: microtubule, tau protein, alzheimer's disease, immune system
• Biological source: HOMO SAPIENS (HUMAN); More
• Total number of polymer chains: 3
• Total formula weight: 47905.14

Authors

Sevcik, J.,Skrabana, R.,Csokova, N.,Dvorsky, R.,Novak, M. (deposition date: 2007-05-22, release date: 2007-12-25, Last modification date: 2024-10-23)

Primary citation

Sevcik, J.,Skrabana, R.,Dvorsky, R.,Csokova, N.,Iqbal, K.,Novak, M.
X-Ray Structure of the Phf Core C-Terminus: Insight Into the Folding of the Intrinsically Disordered Protein Tau in Alzheimer'S Disease.
FEBS Lett., 581:5872-, 2007

PubMed Abstract: The major constituent of Alzheimer's disease paired helical filaments (PHF) core is intrinsically disordered protein (IDP) tau. In spite of a considerable effort, insoluble character of PHF together with inherent physical properties of IDP tau have precluded so far reconstruction of PHF 3D structure by X-ray crystallography or NMR spectroscopy. Here we present first crystallographic study of PHF core C-terminus. Using monoclonal antibody MN423 specific to the tertiary structure of the PHF core, the in vivo PHF structure was imprinted into recombinant core PHF tau. Crystallization of the complex led to determination of the structure of the core PHF tau protein fragment 386TDHGAE391 at 1.65A resolution. Structural analysis suggests important role of the core PHF C-terminus for PHF assembly. It is reasonable to expect that this approach will help to reveal the structural principles underlying the tau protein assembly into PHF and possibly will facilitate rationale drug design for inhibition of Alzheimer neurofibrillary changes.

PubMed: 18061582
DOI: 10.1016/J.FEBSLET.2007.11.067

Experimental method

X-RAY DIFFRACTION (1.65 Å)