OpenSSL SSL_connect: Connection reset by peer in connection to v2.sherpa.ac.uk:443 PuSH - Publication Server of Helmholtz Zentrum München: Structure of the intracellular domain of the amyloid precursor protein in complex with Fe65-PTB2.

PuSH - Publication Server of Helmholtz Zentrum München

Radzimanowski, J.* ; Simon, B.* ; Sattler, M. ; Beyreuther, K.* ; Sinning, I.* ; Wild, K.*

Structure of the intracellular domain of the amyloid precursor protein in complex with Fe65-PTB2.

EMBO Rep. 9, 1134-1140 (2008)
DOI
Open Access Green as soon as Postprint is submitted to ZB.
Cleavage of the amyloid precursor protein (APP) is a crucial event in Alzheimer disease pathogenesis that creates the amyloid-beta peptide (A beta) and liberates the carboxy-terminal APP intracellular domain (AICD) into the cytosol. The interaction of the APP C terminus with the adaptor protein Fe65 mediates APP trafficking and signalling, and is thought to regulate APP processing and A beta generation. We determined the crystal structure of the AICD in complex with the C-terminal phospho-tyrosine-binding (PTB) domain of Fe65. The unique interface involves the NPxY PTB-binding motif and two alpha helices. The amino-terminal helix of the AICD is capped by threonine T-668, an Alzheimer disease-relevant phosphorylation site involved in Fe65-binding regulation. The structure together with mutational studies, isothermal titration calorimetry and nuclear magnetic resonance experiments sets the stage for unterstanding T-668 phosphorylation-dependent complex regulation at a molecular level. A molecular switch model is proposed.
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Publication type Article: Journal article
Document type Scientific Article
Corresponding Author
Keywords Alzheimer disease; amyloid precursor protein; APP intracellular domain; Fe65; phosphotyrosine-binding domain
ISSN (print) / ISBN 1469-221X
e-ISSN 1469-3178
Journal EMBO Reports
Quellenangaben Volume: 9, Issue: 11, Pages: 1134-1140 Article Number: , Supplement: ,
Publisher EMBO Press
Non-patent literature Publications
Reviewing status Peer reviewed
Institute(s) Institute of Structural Biology (STB)