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@ARTICLE{Fluhrer:136321,
author = {Fluhrer, Regina and Kamp, Frits and Grammer, Gudula and
Nuscher, Brigitte and Steiner, Harald and Beyer, Klaus and
Haass, Christian},
title = {{T}he {N}icastrin ectodomain adopts a highly thermostable
structure.},
journal = {Biological chemistry},
volume = {392},
number = {11},
issn = {1437-4315},
address = {Berlin [u.a.]},
publisher = {de Gruyter},
reportid = {DZNE-2020-02643},
pages = {995–1001},
year = {2011},
abstract = {Nicastrin is a type I transmembrane glycoprotein, which is
part of the high molecular weight γ-secretase complex.
γ-Secretase is one of the key players associated with the
generation of Alzheimer's disease pathology, since it
liberates the neurotoxic amyloid β-peptide. Four proteins
Nicastrin, anterior pharynx-defective-1 (Aph-1), presenilin
enhancer-2 (Pen-2) and Presenilin are essential to form the
active γ-secretase complex. Recently it has been shown,
that Nicastrin has a key function in stabilizing the mature
γ-secretase complex and may also be involved in substrate
recognition. So far no structural data for the Nicastrin
ectodomain or any other γ-secretase component are
available. We therefore used Circular Dichroism (CD)
spectroscopy to demonstrate that Nicastrin, similar to its
homologues, the Streptomyces griseus aminopeptidase (SGAP)
and the transferrin receptor (TfR), adopts a thermostable
secondary structure. Furthermore, the Nicastrin ectodomain
has an exceptionally high propensity to refold after thermal
denaturation. These findings provide evidence to further
support the hypothesis that Nicastrin may share evolutionary
conserved properties with the aminopeptidase and the
transferrin receptor family.},
keywords = {Alzheimer Disease: metabolism / Aminopeptidases: chemistry
/ Amyloid Precursor Protein Secretases: chemistry / Cell
Line / Circular Dichroism / Humans / Membrane Glycoproteins:
chemistry / Protein Refolding / Protein Stability / Protein
Structure, Secondary / Protein Structure, Tertiary /
Receptors, Transferrin: chemistry / Streptomyces griseus:
enzymology / Temperature / Membrane Glycoproteins (NLM
Chemicals) / Receptors, Transferrin (NLM Chemicals) /
nicastrin protein (NLM Chemicals) / Amyloid Precursor
Protein Secretases (NLM Chemicals) / Aminopeptidases (NLM
Chemicals)},
cin = {AG Fluhrer / AG Steiner / AG Haass},
ddc = {570},
cid = {I:(DE-2719)1110000-2 / I:(DE-2719)1110000-1 /
I:(DE-2719)1110007},
pnm = {342 - Disease Mechanisms and Model Systems (POF3-342)},
pid = {G:(DE-HGF)POF3-342},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:21848507},
doi = {10.1515/BC.2011.169},
url = {https://pub.dzne.de/record/136321},
}