What does protein aggregation do?
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Protein aggregation is a biological phenomenon in which intrinsically disordered proteins or mis-folded proteins aggregate (i.e., accumulate and clump together) either intra- or extracellularly. Mis-folded protein aggregates are often correlated with diseases.
Why are some proteins more prone to aggregation?
It is well established that certain amino acids influence protein aggregation and that proteins with solvent exposed stretches of high hydrophobicity and a low net charge are aggregation-prone. Indeed, aliphatic amino acids along with basic amino acids were over-represented in physiological aggregates (Unstressed set).
Why does protein aggregation occur?
Protein aggregation can occur through chemical or physical degradation and is dependent on the thermodynamic stability of the protein’s native state. The driving force behind protein aggregation is the reduction in free surface energy by the removal of hydrophobic residues from contact with the solvent.
What is the role of protein aggregation in neurodegeneration?
Neurodegenerative diseases typically involve deposits of inclusion bodies that contain abnormal aggregated proteins. Therefore, it has been suggested that protein aggregation is pathogenic.
Are all protein aggregates toxic?
All pathogenic proteins differ from each other in biological function, primary sequences, and morphologies; however, the proteins are toxic when aggregated.
What protein aggregates in Huntington’s disease?
1.1 Huntington’s Disease Huntington’s disease (HD) is a neurodegenerative disease, caused by the aggregation of the huntingtin (HTT) protein in the human brain nerve cells.
Why is it important to avoid aggregation of proteins during protein extraction?
Proteins are extremely sensitive to solution conditions (i.e., pH and conductivity) and temperature. They also tend to aggregate at high concentrations required for structural studies. This can be a serious problem since protein aggregation can cause artifacts and hamper the biological activity of the target protein.
What is one reason that protein folding intermediates are prone to aggregation?
The intermediates are more prone to aggregate than the unfolded state because in the unfolded state the hydrophobic sidechains are scattered relatively randomly in many small hydrophobic regions, whereas in the partially folded intermediates there will be large patches of contiguous surface hydrophobicity, which will …
What is abnormal protein aggregation?
A common characteristic of many neurodegenerative diseases is protein aggregation due to a failure of clearance mechanism(s). The neurodegenerative disorders featured in the workshop share pathological accumulation in the brain of abnormal protein aggregates or inclusions that contain misfolded proteins.
Can protein misfolding be beneficial?
Furthermore, the term infers that misfolding may generate harmful protein species, which damage the cells that produce them. Such variations in the folding of a polypeptide might either lead to disease by gain of toxic activity or by loss of the native biological function 27.