TY  - JOUR
AU  - Fluhrer, Regina
AU  - Kamp, Frits
AU  - Grammer, Gudula
AU  - Nuscher, Brigitte
AU  - Steiner, Harald
AU  - Beyer, Klaus
AU  - Haass, Christian
TI  - The Nicastrin ectodomain adopts a highly thermostable structure.
JO  - Biological chemistry
VL  - 392
IS  - 11
SN  - 1437-4315
CY  - Berlin [u.a.]
PB  - de Gruyter
M1  - DZNE-2020-02643
SP  - 995–1001
PY  - 2011
AB  - 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.
KW  - Alzheimer Disease: metabolism
KW  - Aminopeptidases: chemistry
KW  - Amyloid Precursor Protein Secretases: chemistry
KW  - Cell Line
KW  - Circular Dichroism
KW  - Humans
KW  - Membrane Glycoproteins: chemistry
KW  - Protein Refolding
KW  - Protein Stability
KW  - Protein Structure, Secondary
KW  - Protein Structure, Tertiary
KW  - Receptors, Transferrin: chemistry
KW  - Streptomyces griseus: enzymology
KW  - Temperature
KW  - Membrane Glycoproteins (NLM Chemicals)
KW  - Receptors, Transferrin (NLM Chemicals)
KW  - nicastrin protein (NLM Chemicals)
KW  - Amyloid Precursor Protein Secretases (NLM Chemicals)
KW  - Aminopeptidases (NLM Chemicals)
LB  - PUB:(DE-HGF)16
C6  - pmid:21848507
DO  - DOI:10.1515/BC.2011.169
UR  - https://pub.dzne.de/record/136321
ER  -