6oc9 | pdb_00006oc9

S8 phosphorylated beta amyloid 40 fibrils

spinqualitylabelsall models 6oc9, 10 NMR models Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 6oc9 is a 10 chain structure. Full experimental information is available from OCA. For a guided tour on the structure components use FirstGlance. Ligands: 2PO Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Disease [A4_HUMAN] Defects in APP are the cause of Alzheimer disease type 1 (AD1) [MIM:104300]. AD1 is a familial early-onset form of Alzheimer disease. It can be associated with cerebral amyloid angiopathy. Alzheimer disease is a neurodegenerative disorder characterized by progressive dementia, loss of cognitive abilities, and deposition of fibrillar amyloid proteins as intraneuronal neurofibrillary tangles, extracellular amyloid plaques and vascular amyloid deposits. The major constituent of these plaques is the neurotoxic amyloid-beta-APP 40-42 peptide (s), derived proteolytically from the transmembrane precursor protein APP by sequential secretase processing. The cytotoxic C-terminal fragments (CTFs) and the caspase-cleaved products such as C31 derived from APP, are also implicated in neuronal death. Defects in APP are the cause of cerebral amyloid angiopathy APP-related (CAA-APP) [MIM:605714]. A hereditary localized amyloidosis due to amyloid-beta A4 peptide(s) deposition in the cerebral vessels. The principal clinical characteristics are recurrent cerebral and cerebellar hemorrhages, recurrent strokes, cerebral ischemia, cerebral infarction, and progressive mental deterioration. Patients develop cerebral hemorrhage because of the severe cerebral amyloid angiopathy. Parenchymal amyloid deposits are rare and largely in the form of pre-amyloid lesions or diffuse plaque-like structures. They are Congo red negative and lack the dense amyloid cores commonly present in Alzheimer disease. Some affected individuals manifest progressive aphasic dementia, leukoencephalopathy, and occipital calcifications. Function [A4_HUMAN] Functions as a cell surface receptor and performs physiological functions on the surface of neurons relevant to neurite growth, neuronal adhesion and axonogenesis. Involved in cell mobility and transcription regulation through protein-protein interactions. Can promote transcription activation through binding to APBB1-KAT5 and inhibits Notch signaling through interaction with Numb. Couples to apoptosis-inducing pathways such as those mediated by G(O) and JIP. Inhibits G(o) alpha ATPase activity (By similarity). Acts as a kinesin I membrane receptor, mediating the axonal transport of beta-secretase and presenilin 1. Involved in copper homeostasis/oxidative stress through copper ion reduction. In vitro, copper-metallated APP induces neuronal death directly or is potentiated through Cu(2+)-mediated low-density lipoprotein oxidation. Can regulate neurite outgrowth through binding to components of the extracellular matrix such as heparin and collagen I and IV. The splice isoforms that contain the BPTI domain possess protease inhibitor activity. Induces a AGER-dependent pathway that involves activation of p38 MAPK, resulting in internalization of amyloid-beta peptide and leading to mitochondrial dysfunction in cultured cortical neurons. Provides Cu(2+) ions for GPC1 which are required for release of nitric oxide (NO) and subsequent degradation of the heparan sulfate chains on GPC1. Beta-amyloid peptides are lipophilic metal chelators with metal-reducing activity. Bind transient metals such as copper, zinc and iron. In vitro, can reduce Cu(2+) and Fe(3+) to Cu(+) and Fe(2+), respectively. Beta-amyloid 42 is a more effective reductant than beta-amyloid 40. Beta-amyloid peptides bind to lipoproteins and apolipoproteins E and J in the CSF and to HDL particles in plasma, inhibiting metal-catalyzed oxidation of lipoproteins. Beta-APP42 may activate mononuclear phagocytes in the brain and elicit inflammatory responses. Promotes both tau aggregation and TPK II-mediated phosphorylation. Interaction with Also bind GPC1 in lipid rafts. Appicans elicit adhesion of neural cells to the extracellular matrix and may regulate neurite outgrowth in the brain (By similarity). The gamma-CTF peptides as well as the caspase-cleaved peptides, including C31, are potent enhancers of neuronal apoptosis. N-APP binds TNFRSF21 triggering caspase activation and degeneration of both neuronal cell bodies (via caspase-3) and axons (via caspase-6). Publication Abstract from PubMed The structural polymorphism in beta-amyloid (Abeta) plaques from Alzheimer disease (AD) has been recognized as an important pathological factor. Plaques from sporadic AD patients contain fibrillar deposits of various amyloid proteins/peptides, including posttranslational modified Abeta (PTM-Abeta) subtypes. Although many PTM-Abetas were shown to accelerate the fibrillation process, increase neuronal cytotoxicity of aggregates, or enhance the stability of fibrils, the contribution of PTM-Abetas to structural polymorphisms and their pathological roles remains unclear. We report here the NMR-based structure for the Ser-8-phosphorylated 40-residue Abeta (pS8-Abeta40) fibrils, which shows significant difference to the wild-type fibrils, with higher cross-seeding efficiency and thermodynamic stability. Given these physicochemical properties, the structures originated from pS8-Abeta40 fibrils may potentially dominate the polymorphisms in the mixture of wild-type and phosphorylated Abeta deposits. Our results imply that Abeta subtypes with "seeding-prone" properties may influence the polymorphisms of amyloid plaques through the cross-seeding process. Molecular structure of an N-terminal phosphorylated beta-amyloid fibril.,Hu ZW, Vugmeyster L, Au DF, Ostrovsky D, Sun Y, Qiang W Proc Natl Acad Sci U S A. 2019 May 16. pii: 1818530116. doi:, 10.1073/pnas.1818530116. PMID:31097588 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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