Question

The genetically engineered proteins that accumulate in bacterial inclusion bodies (Fig. 5-2) form amyloid structures. Such proteins are often difficult to recover in functional form from the bacteria. Explain.

Short answer

The individual protein might be difficult to be separated from the accumulation and dissolved in the aqueous environment, due to the hydrophobic interactions and hydrogen bonds in and between the protein molecules. Also, the misfolded or partially folded protein could be difficult to recover in its native and functional form.

Step-by-step solution

Amyloid structure formed by protein accumulation

The three-dimensional structure of proteins allows its hydrophobic residues to extend towards the interior of the protein, that is, far away from the aqueous solvent; the hydrophilic residues extend towards the surface of the protein, shielding the inner hydrophobic core from the outer aqueous environment.

When the protein does not fold properly, the three-dimensional stable protein structure gets disrupted. This results in the hydrophobic amino acid residues getting positioned at the surface of the protein.

The presence of such hydrophobic residues makes the surface ‘sticky’ and allows the misfolded or partially folded protein to aggregate with the hydrophobic sticky surfacesof other such misfolded or partially folded proteins. Such accumulated structures, sometimes, exhibit the structure of the accumulation of amyloid β proteins.

Accumulated proteins are difficult to recover in functional form

In order to recover the proteins in their functional form, the accumulated proteins first need to be disaggregated and then folded correctly. The processes involved in the recovery of the protein in its functional form, however, is often not easy due to the following reasons:

1. The hydrophobic interactions and the hydrogen bonds inside and between the proteins do not allow individual protein to be separated and dissolved in aqueous environment.
2. The misfolded or partially folded protein may not be easily folded correctlyto form the native and functional structure of the protein.