The nicastrin ectodomain adopts a highly thermostable structure
| Autor: | Gudula Grammer, Klaus Beyer, Regina Fluhrer, Brigitte Nuscher, Harald Steiner, Frits Kamp, Christian Haass |
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| Jazyk: | angličtina |
| Rok vydání: | 2011 |
| Předmět: |
chemistry [Membrane Glycoproteins]
Circular dichroism Clinical Biochemistry Nicastrin Transferrin receptor chemistry [Receptors Transferrin] Aminopeptidases Biochemistry Aminopeptidase Protein Refolding Protein Structure Secondary Presenilin chemistry [Aminopeptidases] Cell Line nicastrin protein Alzheimer Disease ddc:570 Receptors Transferrin Humans ddc:610 APH-1 Molecular Biology Protein secondary structure Membrane Glycoproteins biology Protein Stability Circular Dichroism enzymology [Streptomyces griseus] Streptomyces griseus Temperature Protein Structure Tertiary Ectodomain chemistry [Amyloid Precursor Protein Secretases] biology.protein Amyloid Precursor Protein Secretases metabolism [Alzheimer Disease] |
| Zdroj: | Biological chemistry 392(11), 995–1001 (2011). doi:10.1515/BC.2011.169 |
| DOI: | 10.1515/BC.2011.169 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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