Journal Article

DZNE-2020-02643

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png The Nicastrin ectodomain adopts a highly thermostable structure.

Fluhrer, R. (First author)DZNE* ; Kamp, F. ; Grammer, G. ; Nuscher, B. ; Steiner, H.DZNE* ; Beyer, K. ; Haass, C. (Last author)DZNE*

2011
de Gruyter Berlin [u.a.]

This record in other databases:    

Please use a persistent id in citations: doi:10.1515/BC.2011.169

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.

Keyword(s): Alzheimer Disease: metabolism (MeSH) ; Aminopeptidases: chemistry (MeSH) ; Amyloid Precursor Protein Secretases: chemistry (MeSH) ; Cell Line (MeSH) ; Circular Dichroism (MeSH) ; Humans (MeSH) ; Membrane Glycoproteins: chemistry (MeSH) ; Protein Refolding (MeSH) ; Protein Stability (MeSH) ; Protein Structure, Secondary (MeSH) ; Protein Structure, Tertiary (MeSH) ; Receptors, Transferrin: chemistry (MeSH) ; Streptomyces griseus: enzymology (MeSH) ; Temperature (MeSH) ; Membrane Glycoproteins ; Receptors, Transferrin ; nicastrin protein ; Amyloid Precursor Protein Secretases ; Aminopeptidases

---

Contributing Institute(s):

1. Signal Peptide Peptidases as Models for γ-Secretase (AG Fluhrer)
2. Biochemistry of γ-Secretase (AG Steiner)
3. Molecular Neurodegeneration (AG Haass)

Research Program(s):

1. 342 - Disease Mechanisms and Model Systems (POF3-342) (POF3-342)

Appears in the scientific report 2011

---

Database coverage:
; BIOSIS Previews ; Clarivate Analytics Master Journal List ; Current Contents - Life Sciences ; Ebsco Academic Search ; IF < 5 ; JCR ; NCBI Molecular Biology Database ; Nationallizenz ; SCOPUS ; Science Citation Index ; Science Citation Index Expanded ; Web of Science Core Collection

---