4f37

Structure of the tethered N-terminus of Alzheimer's disease A peptide

spinqualitylabelsall models 4f37, resolution 2.57Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 4f37 is a 6 chain structure with sequence from Escherichia coli and Mus musculus. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function IMM7_ECOLX This protein is able to protect a cell, which harbors the plasmid ColE7 encoding colicin E7, against colicin E7, it binds specifically to the DNase-type colicin and inhibits its bactericidal activity. Dimeric ImmE7 may possess a RNase activity that cleaves its own mRNA at a specific site and thus autoregulates translational expression of the downstream ceiE7 gene as well as degradation of the upstream ceaE7 mRNA. Publication Abstract from PubMed Alzheimer's disease is the most common form of dementia in humans and is related to the accumulation of the amyloid-beta (Abeta) peptide and its interaction with metals (Cu, Fe and Zn) in the brain. Crystallographic structural information about Abeta peptide deposits and the details of the metal binding site is limited due to the heterogeneous nature of aggregation states formed by the peptide. Here we present a crystal structure of Abeta residues 1-16 fused to the N-terminus of the E. coli immunity protein Im7, and stabilized with the Fab fragment of the anti-Abeta N-terminal antibody WO2. The structure demonstrates that Abeta residues 10-16, which are not in complex with the antibody, adopt a mixture of local polyproline II (PPII) helix and turn type conformations, enhancing co-operativity between the two adjacent histidine residues His13 and His14. Furthermore, this relatively rigid region of Abeta (residues 10-16) appear as an almost independent unit available for trapping metal ions and provides a rationale for the His13-metal-His14 coordination in the Abeta1-16 fragment implicated in Abeta metal binding. This novel structure therefore has the potential to provide a foundation for investigating the effect of metal ion binding to Abeta and illustrates a potential target for development of future Alzheimer's disease therapeutics aimed at stabilizing the N-terminal monomer structure, in particular residues His13 and His14, and preventing Abeta metal binding-induced neurotoxicity. (c) Proteins 2013;. (c) 2013 Wiley Periodicals, Inc. Structural studies of the tethered N-terminus of the Alzheimer's disease Abeta peptide.,Nisbet RM, Nuttall SD, Robert R, Caine JM, Dolezal O, Hattarki M, Pearce LA, Davydova N, Masters CL, Varghese JN, Streltsov VA Proteins. 2013 Apr 23. doi: 10.1002/prot.24312. PMID:23609990 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Colicin immunity protein 3D structures Monoclonal Antibodies 3D structures

Proteopedia Page Contributors and Editors (what is this?)

OCA