Key Concepts of Section 3.2

• The primary structure (amino acid sequence) of a protein determines its three-dimensional structure, which determines its function. In short, function derives from structure; structure derives from sequence.

• Because protein function derives from protein structure, newly synthesized proteins must fold into the correct shape to function properly.

• The planar structure of the peptide bond limits the number of conformations a polypeptide can have (see Figure 3-15).

• The amino acid sequence of a protein dictates its folding into a specific three-dimensional conformation, the native state. Proteins will unfold, or denature, if treated under conditions that disrupt the noncovalent interactions stabilizing their three-dimensional structures.

• There are two broad classes of non-native conformations seen in misfolded or denatured proteins: (1) monomeric unfolded or denatured structures and (2) aggregates, which can either be amorphous or have a well-organized structure.

• Protein folding in vivo occurs with assistance from ATP-dependent chaperones. Chaperones can influence proteins in several ways, including preventing misfolding and aggregation, facilitating proper folding, and maintaining an appropriate, stable structure required for subsequent protein activity (see Figure 3-17).

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• There are two broad classes of chaperones: (1) molecular chaperones, which bind to a short segment of a substrate protein, and (2) chaperonins, which form folding chambers in which all or part of an unfolded protein can be sequestered, giving it time and an appropriate environment to fold properly. Cycles of ATP binding and hydrolysis, followed by exchange of the ADP produced with a new ATP molecule, play key roles in the mechanisms of protein folding by chaperones.

• Many misfolded or denatured proteins can form well-organized aggregates, called amyloid fibrils, made by short stretches of polypeptide that form a long array of β sheets nearly perpendicular to the fibril axis, called a cross-β structure. Formation of amyloid fibrils that are resistant to degradation by diverse enzymes is associated with dozens of diseases called amyloidoses. Examples include the neurodegenerative diseases Alzheimer’s disease and Parkinson’s disease.