Protein aggregation

In molecular biology, protein aggregation is a phenomenon in which intrinsically-disordered or mis-folded proteins aggregate (i.e., accumulate and clump together) either intra- or extracellularly. Protein aggregates have been implicated in a wide variety of diseases known as amyloidoses, including ALS, Alzheimer's, Parkinson's and prion disease. After synthesis, proteins typically fold into a particular three-dimensional conformation that is the most thermodynamically favorable: their native state. This folding process is driven by the hydrophobic effect: a tendency for hydrophobic (water-fearing) portions of the protein to shield themselves from the hydrophilic (water-loving) environment of the cell by burying into the interior of the protein. Thus, the exterior of a protein is typically hydrophilic, whereas the interior is typically hydrophobic. Protein structures are stabilized by non-covalent interactions and disulfide bonds between two cysteine residues. The non-covalent interactions include ionic interactions and weak van der Waals interactions. Ionic interactions form between an anion and a cation and form salt bridges that help stabilize the protein. Van der Waals interactions include nonpolar interactions (i.e. London dispersion force) and polar interactions (i.e. hydrogen bonds, dipole-dipole bond). These play an important role in a protein's secondary structure, such as forming an alpha helix or a beta sheet, and tertiary structure. Interactions between amino acid residues in a specific protein are very important in that protein's final structure. When there are changes in the non-covalent interactions, as may happen with a change in the amino acid sequence, the protein is susceptible to misfolding or unfolding. In these cases, if the cell does not assist the protein in re-folding, or degrade the unfolded protein, the unfolded/misfolded protein may aggregate, in which the exposed hydrophobic portions of the protein may interact with the exposed hydrophobic patches of other proteins.