Sandbox Reserved 200: Difference between revisions

<Structure load='1A2W' size='400' frame='true' align='right' caption='Ribonuclease A Dimer' scene='Sandbox_Reserved_200/Minor_dimer/2' />

Ribonuclease A has both a major and <scene name='Sandbox_Reserved_200/Minor_dimer/2'>Minor dimer</scene> which are very similar to one another. Though they are similar, they are formed by different types of 3D domain swapping.  3D domain swapping occurs when identical domains are interchanged.  The <scene name='Sandbox_Reserved_200/Major_dimer/11'>Major dimer</scene> is formed by 3D domain swapping the β-strand of the C-terminus.<ref name="liu98"/> The minor dimer, on the other hand, is formed by 3D domain swapping its α-helix of the N-terminus <ref name="liu98"/>.  Domain swapping is extremely specific and can only occur at the <scene name='Sandbox_Reserved_200/Major_dimer/10'>C-terminus</scene> or the <scene name='Sandbox_Reserved_200/Major_dimer/9'>N-terminus</scene>.

The two domains of the dimer are linked via the hinge loop.<ref name="liul"/>.  In the major dimer, the hinge loop is composed of residues 112-115. In the minor dimer, the hinge loop is composed of residues 16-22.<ref name="liul"/>  The most important component of the hinge loops is Ala19.  <scene name='Sandbox_Reserved_200/Minor_dimer_hinge/1'>Ala19</scene> is the reason that the hinge loops are so flexible . This flexibility allows the dimers to adopt different orientations, for example the major and minor structures.<ref name="liu98"/>   

[http://en.wikipedia.org/wiki/Alzheimer%27s_disease Alzheimer’s disease] is a terminal disease that slowly degenerates the brain.  One of the possible causes of Alzheimer’s is [http://en.wikipedia.org/wiki/Amyloid amyloid] deposits throughout the brain.  Though RNasa A oligomers are not the amyloid deposits that cause Alzheimer’s the folding of these oligomers gives clues towards the formation of amyloid deposits responsible for Alzheimer’s.

The 3D domain swapping has many similarities with the formation of amyloid fibers.  Both are highly specific reactions coming from only one type of monomer and these reactions can form linear aggregates. <ref name="liu01"/>  These aggregates of proteins are formed by hydrogen bonding at the hinge loops which form an antiparalell β-pleated sheet. <ref name="liu01"/>  This most commonly happens with the major dimer.  Liu suggests that all proteins are capable of forming aggregates by domain swapping as long as they are in high concentration and partially destabilized. <ref name="liu01"/>  As 3D domain swapping becomes more understood, it will offer insight to the amyloid formation in Alzheimer’s patients.