Journal of Biochemical Sciences

Protein Folding

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Protein folding is a crucial biological occurrence in which a linear sequence of amino acids, produced by ribosomes, changes into a three-dimensional shape. This change is essential for the protein's biological activity since its configuration dictates its function inside the cell. Proteins that do not fold properly can result in inactive or potentially harmful aggregates, linked to several diseases, including neurodegenerative conditions like Alzheimer’s and Parkinson’s disease.

Protein folding starts immediately after the amino acid chain is formed. The order of amino acids, referred to as the primary structure, dictates the ultimate three-dimensional shape. The folding procedure takes a hierarchical route, beginning with the creation of secondary structures, including alpha helices and beta sheets, which are supported by hydrogen bonds. These formations then fold into a dense tertiary structure, creating a functional protein. Certain proteins additionally form quaternary structures that consist of several polypeptide chains.

Multiple factors influence protein folding, such as hydrophobic interactions, hydrogen bonds, van der Waals forces, and electrostatic attractions. The hydrophobic effect is crucial because nonpolar amino acids usually cluster in the protein's interior, protecting themselves from the watery surroundings. Furthermore, molecular chaperones help in the folding process by stopping misfolding and aggregation.

Misfolded proteins may lose their functionality or create toxic aggregates, resulting in serious diseases. Protein misfolding is associated with conditions like Alzheimer's disease, which involves the buildup of amyloid plaques in the brain, and Parkinson's disease, marked by misfolded alpha-synuclein proteins. Prion diseases, like Creutzfeldt–Jakob disease, arise from improper protein folding, in which misfolded proteins cause normal proteins to take on an aberrant structure.