Sandbox Reserved 197: Difference between revisions

Another important feature of the folding of RNase A is the presence of four disulfide bonds.  These bonds contribute to the thermal stability and the rate of folding of RNase A.  The residues involved in these linkages include <scene name='Sandbox_Reserved_197/Cys26-cys84/4'>Cys26-Cys84</scene>, <scene name='Sandbox_Reserved_197/Cys58-cys110/4'>Cys58-Cys110</scene>, <scene name='Sandbox_Reserved_197/40-95_disulfide_native_form/4'>Cys40-Cys95</scene>, and <scene name='Sandbox_Reserved_197/Cys65-cys72/5'>Cys65-Cys72</scene>.  Cys26-Cys84 and Cys58-Cys110 create an interaction between an α-helix and a β-sheet.  This connection is the main contributor to the thermodynamic stability.  RNase A actually has a rate-determining three-disulfide intermediate.  An analog of this, <scene name='Sandbox_Reserved_197/C40-95a_variant/6'>C[40,95]A</scene>, shows RNase A, missing the disulfide bond, Cys40-Cys95, that would normally occur here.  As you can see in the variant, there are only 3 disulfide bonds present, shown in red.

Protein folding, along with its inhibitions, is immensely important to the human.  Such diseases as ALS, Alzheimer's Disease, and Parkinson's Disease can all be traced back to the protein.  Proteins can form aberrant aggregates when they do not fold correctly.  This abnormaility can be fatally toxic to the human nerve cells.  During folding, proteins sometimes make a mistake.  In the case of these aggregates, the mistake exposes "sticky" hydrophobic patches that can cause several proteins to stick to one another.  In the future researchers hope to design drugs that combat this mistake in the protein folding.  The use of ribonuclease A in protein folding research has been an instrumental feature in designing experiments to determine these "misfolding" snapshots and in developing therapies to prevent this problem in the future.

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