Conformation amyloid-/?-peptide

Lee JP, Stimson ER, Ghilardi JR, Mantyh PW, Lu Y-A, Felix AM, Llanos W, Behbin A, Cummings M, Criekinge MV, Timms W, Maggio JE. 1H NMR of A(i amyloid peptide congeners in water solution. Conformational changes correlate with plaque competence. Biochemistry 1995 34 5191-5200. 

Figure 10-5. Representative conformations of the (5 amyloid peptide (10-42) under different pH conditions. The conformations were obtained as centroids of the most populated clusters from the replica-exchange CPHMD folding simulations [43, 44]. The N-terminal residues 10-28 are shown in blue the C-terminal residues 29-42 are shown in red. In the most aggregation-prone state (pH 6), the side chains of the central hydrophobic cluster Leu-17, Val-18, Phe-19, Phe-20 and Ala-21 are shown as van der Waals spheres in pink, grey, cyan, purple and green, respectively...

Because conformational epitopes are not easily mimicked with linear peptides, which can elicit nonspecific antibodies, several alternative strategies such as synthetic cyclic peptides have been developed [see e.g., (18)]. A similar conformational restriction was seemingly achieved with a P-amyloid peptide that was anchored to the surface of liposomes via hydrophobic tails introduced at its both N- and C-termini. The reconstituted peptide proved highly immunogenic and elicited antibodies that could significantly prevent amyloid plaque formation in a model system (70). 

Liu D, Xu Y, Feng Y, Liu H, Shen X, Chen K, Ma J, Jiang H. Inhibitor discovery targeting the intermediate structure of beta-amyloid peptide on the conformational transition pathway implications in the aggregation mechaitism of beta-amyloid peptide. Biochemistry 2006 45 10963-10972. 

Prion and scrapie diseases are linked with the conformational transition of normally monomeric a-helical cellular prion protein, PrP, to a B-sheet-rich pathogenic form, PrP , which is prone to aggregation. A similar conformational transition of the normal cellular form of a-helical amyloid peptide (aAP (1-40)) into the disease-specific largely B-sheet form of amyloid peptide (BAP (1-40)) occurs in Alzheimer s disease, which results in amyloid deposits (Monaco et al., 2006). So far more than 19 different mutations in the human PrP gene have been linked with inherited prion diseases (Monaco et al., 2006). However, the molecular event triggering the spontaneous conversion of wild-type and... 

Both brain function and composition are affected by dietary boron (Nielsen 1996, Pen-land 1998). Assessments of both animal models and humans found that boron deprivation results in decreased brain electrical activity similar to that observed in nonspecific malnutrition. Boron deprivation also resulted in poorer performance in tasks of motor speed and dexterity, attention, and short-term memory in humans. Increased copper and calcium concentrations in total brain and increased phosphorus in the cerebellum have been found in boron-deprived rats. Boron reportedly can restore the a-hel-ical conformation of (l-amyloid peptide (1 -40) disrupted by aluminum (Ramakrishna etal. 1997). 

Specific labeling normally refers to incorporate a non-uniformly N labeled amino acid into a polypeptide/protein or a ligand at a certain position. It requires solid-phase peptide synthesis or chemical synthesis. This approach has been used extensively to study amyloid peptides, membrane peptides, and GPCR ligand conformation [93-99]. 

Several studies have confirmed that beta-amyloid peptides undergo structural transitions to form mobile oligomers that are composed of a particular aggregation-prone conformation of the peptide. Once the oligomers exceed critical size, they nucleate to form protofilaments which finally transform to crossbeta sheets or fibrils that are responsible for the formation of extracellular amyloid plaques. The tendency to form beta-strands is due to its ability to stabilize the beta-turn by a salt bridge between residues aspartic acid-23 and lysine-28 and the hydrophobic region. 

Yahi N, Aulas A, Fantini J. How cholesterol constrains glycoKpid conformation for optimal recognition of Alzheimer s beta amyloid peptide (Abetal-40). PloS One. 2010 5(2) e9079. 

Fantini J, Yahi N, Garmy N. Cholesterol accelerates the binding of Alzheimer s beta-amyloid peptide to gan-ghoside GMl through a universal hydrogen-bond-dependent sterol tuning of glycoHpid conformation. Front Physiol. 2013 4 120. 

Kagan BL, Thundimadathil J. Amyloid peptide pores and the beta sheet conformation. Adv Exp Med Biol. 

In the search for fibril formation inhibitors, the self-association to form amyloid fibrils of the A(3 peptides containing 40 and 42 amino acids can be treated as a coupled protein folding and polymerization process passing through multiple intermediate peptide species. The in vitro challenge is (1) to identify the various conformational forms and... 

The failure of proteins to fold into their functional forms can occasionally lead to "misfolding" or "conformational" diseases.140 Many of these diseases are associated with the formation of amyloid protein, an insoluble material that is deposited as fibrils or plaques in different tissues and organs of the body. They include amyloid Ap protein as the major constituent of the plaques in Alzheimer patients, PrPc associated with neuro-degenerative diseases, a-synuclein (AS) associated with Parkinson s diseases, transthyretin (TTR) as a homotetrameric protein that is involved in the transport of thyroid hormones and retinol in human serum. In particular, the Ap protein is a peptide of 39-43 amino acids that is the... 

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