From Globular Proteins to Amyloids

Description

From Globular Proteins to Amyloids proposes a model and mechanism for explaining protein misfolding. Concepts presented are based on a model originally intended to show how proteins attain their native conformations. This model is quantitative in nature and founded upon arguments derived from information theory. It facilitates prediction and simulation of the amyloid fibrillation process, also identifying the progressive changes that occur in native proteins that lead to the emergence of amyloid aggregations. Introduces basic rules for protein folding, along with the conditions that result in misfoldingPresents research that lies in treating the aqueous environment as a continuum rather than a set of individual water molecules (i.e. the classic representation)Provides practical applications for helping the prevention of amyloidosis and improving drug design From Globular Proteins to Amyloids Copyright Contributors Preface References Introduction References 1 . Description of the fuzzy oil drop model Amyloids as seen from the perspective of the FOD model References 2 . Folding with active participation of water References 3 . Information encoded in protein structure References 4 . Globular or ribbon-like micelle Effect of the aqueous environment on intramolecular processes The effect of proteins influence on the water structuralization Amyloid structures The protein is an intelligent micelle References 5 . Proteins structured as spherical micelles Type III antifreeze proteins Titin Ultrafast-folding proteins Stabilization in the presence of disulfide bonds Proteins consistent with the theoretical model—spherical micelles Counter-example—prefoldin References 6 . Local discordance 6.A . The active site in a single-chain enzyme Lysozyme Ribonuclease References 6.B . Protein-protein interaction encoded as an exposure of hydrophobic residues on the surface Individual chains DNA binding References 6.C . Ligand binding cavity encoded as a local hydrophobicity deficiency References 7 . Solenoid – An amyloid under control Antifreeze proteins represented by protein extracted from Flavobacterum frigoris PS1 found in the Antarctic region Lyase family represented by pectate lyase “Perfect” solenoid Flattened double-walled solenoid Conclusions and discussion References 8 . Composite structures Single-chian enzyme consisting of three domains Analysis of the molecule as a whole Domains treated as independent structural units Homodimer enzyme Analysis of chains and domains regarded as standalone structures Domains Conclusions and discussion References 9 . Non-amyloid structure of the Aβ(1–42) polypeptide in presence of a permanent chaperone 9.A . Complexes Aβ(1–42) polypeptide with non-protein molecules Structural characteristics of Aβ(1–42) fragments in complex with selected compounds Assessment of the hydrophobic core structure in non-amyloid forms of Aβ(1–42) Analysis of the 11–16 fragment Analysis of the 16–22 fragment Analysis of the 22–28 fragment Unusual structure observed in 1HZ3 – 10-35 fragment of Aβ(1–42) forming a random coil, together with an external factor (tr ... Common characteristics of all discussed proteins Comprehensive analysis Conclusions and discussion References 9.B . Structure of selected fragments of Aβ(1–42) in complex with other proteins Non-amyloid conformations of Aβ(1–42) fragments Aβ(17–27) and Aβ(16–28) in complex with lipocain Aβ(16–40) in complex with phage-display selected affibody protein Z(Aβ3) Aβ(1–40) in complex with polyphenol ε-viniferin glucoside (EVG) Aβ(1–21) in complex with the JEF ligand Aβ(18–41) fragment inserted as the antigen receptor variable domain in shark immunoglobulin Discussion and conclusions References 10 . Amyloids identification based on fuzzy oil drop model References 10.A . Amyloid as a ribbon-like micelle Amyloid Aβ(1–40) peptide with the Osaka mutation (E22Δ) Aβ(11–42) amyloid Prion amyloid In silico experiment References 10.B . Analysis of alternative conformations of the Aβ(1–40) amyloid protein Alternative structural forms of polypeptide Aβ(1–40) polypeptide which includes the Osaka mutation Values of RD and correlation coefficients may be calculated for the entire protein (polypeptide), but also for selected fra ... Comparative analysis of protein structures generated using folding simulation software References 10.C . Specificity of amino acid sequence and its role in secondary and supersecondary structure generation Short fragments of polypeptide playing the ole of linkers between β-strands belonging to β-sheets Short peptides Alternative structures solve the problem of minimization of the hydrophobic area on the surface generating the ribbon-like ... References 11 . Anti-amyloid drug design References 12 . The hypothetical amyloid transformation of transthyretin References . Summary: protein is an intelligent micelle Influence of protein on water environment Influence of water environment on amyloid transformation Protein is an intelligent micelle References Index A B C D E F G H I J K L M N O P Q R S T U V W