Skip to main page content
Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2012 Jun 12;586(12):1687-92.
doi: 10.1016/j.febslet.2012.04.062. Epub 2012 May 11.

Dimeric Structure of Transmembrane Domain of Amyloid Precursor Protein in Micellar Environment

Affiliations
Free article

Dimeric Structure of Transmembrane Domain of Amyloid Precursor Protein in Micellar Environment

Kirill D Nadezhdin et al. FEBS Lett. .
Free article

Abstract

Some pathogenic mutations associated with Alzheimer's disease are thought to affect structural-dynamic properties and the lateral dimerization of amyloid precursor protein (APP) in neuron membrane. Dimeric structure of APP transmembrane fragment Gln(686)-Lys(726) was determined in membrane-mimicking dodecylphosphocholine micelles using high-resolution NMR spectroscopy. The APP membrane-spanning α-helix Lys(699)-Lys(724) self-associates in a left-handed parallel dimer through extended heptad repeat motif I(702)X(3)M(706)X(2)G(709)X(3)A(713)X(2)I(716)X(3)I(720)X(2)I(723), whereas the juxtamembrane region Gln(686)-Val(695) constitutes the nascent helix, also sensing the dimerization. The dimerization mechanism of APP transmembrane domain has been described at atomic resolution for the first time and is important for understanding molecular events of APP sequential proteolytical cleavage resulting in amyloid-β peptide.

Similar articles

See all similar articles

Cited by 28 articles

See all "Cited by" articles

Publication types

Associated data

LinkOut - more resources

Feedback