2BP4

Zinc-binding domain of Alzheimer's disease amyloid beta-peptide in TFE-water (80-20) solution

Replaces:  1O6N

Summary for 2BP4

• Entry DOI: 10.2210/pdb2bp4/pdb
• Related: 1AAP 1AMB 1AMC 1AML 1BA4 1BA6 1BJB 1BJC 1BRC 1CA0 1HZ3 1IYT 1MWP 1O6N 1OWT 1QCM 1QWP 1QXC 1QYT 1TAW 1TKN 1UO7 1UO8 1UOA 1UOI 2BOM
• Descriptor: AMYLOID BETA A4 PROTEIN (1 entity in total)
• Functional Keywords: helix, alzheimer's disease, amyloid, amyloid peptide, beta-amyloid protein
• Biological source: HOMO SAPIENS (HUMAN)
• Cellular location: Membrane; Single-pass type I membrane protein: P05067
• Total number of polymer chains: 1
• Total formula weight: 1960.05

Authors

Zirah, S.,Kozin, S.A.,Mazur, A.K.,Blond, A.,Cheminant, M.,Segalas-Milazzo, I.,Debey, P.,Rebuffat, S. (deposition date: 2005-04-18, release date: 2005-04-21, Last modification date: 2024-05-15)

Primary citation

Zirah, S.,Kozin, S.A.,Mazur, A.K.,Blond, A.,Cheminant, M.,Segalas-Milazzo, I.,Debey, P.,Rebuffat, S.
Structural Changes of Region 1-16 of the Alzheimer Disease Amyloid Beta-Peptide Upon Zinc Binding and in Vitro Aging.
J.Biol.Chem., 281:2151-, 2006

PubMed Abstract: Amyloid deposits within the cerebral tissue constitute a characteristic lesion associated with Alzheimer disease. They mainly consist of the amyloid peptide Abeta and display an abnormal content in Zn(2+) ions, together with many truncated, isomerized, and racemized forms of Abeta. The region 1-16 of Abeta can be considered the minimal zinc-binding domain and contains two aspartates subject to protein aging. The influence of zinc binding and protein aging related modifications on the conformation of this region of Abeta is of importance given the potentiality of this domain to constitute a therapeutic target, especially for immunization approaches. In this study, we determined from NMR data the solution structure of the Abeta-(1-16)-Zn(2+) complex in aqueous solution at pH 6.5. The residues His(6), His(13), and His(14) and the Glu(11) carboxylate were identified as ligands that tetrahedrally coordinate the Zn(II) cation. In vitro aging experiments on Abeta-(1-16) led to the formation of truncated and isomerized species. The major isomer generated, Abeta-(1-16)-l-iso-Asp(7), displayed a local conformational change in the His(6)-Ser(8) region but kept a zinc binding propensity via a coordination mode involving l-iso-Asp(7). These results are discussed here with regard to Abeta fibrillogenesis and the potentiality of the region 1-16 of Abeta to be used as a therapeutic target.

PubMed: 16301322
DOI: 10.1074/JBC.M504454200

Experimental method

SOLUTION NMR