Unlocking the secrets of PARKIN

 

Parkin is a protein that is associated with the PARK2 gene.  Mutations of the Parkin protein are associated with young on-set and familial forms of Parkinson’s.  The role of Parkin in cells is to regulate the function of the mitochondria, or the little energy furnace of the cell. Mutations in the Parkin gene lead to instability of the Parkin protein which can be very debilitating in nerve cells, a mechanism that is not yet fully understood.

One of the roles of Parkin is to remove damaged proteins in the mitochondrial outer membrane and eliminate them.  Research suggests that problems in this pathway may be the cause of Parkinson’s.   Parkin also has other roles in cell signaling as well as in suppressing tumors.  With so many biological roles, understanding how Parkin interacts in so many domains is essential.

In order to investigate some of these interactions, two young researchers at the MRC Laboratory of Molecular Biology in Cambridge, England, have crystallized a form of human Parkin into a three dimensional structure.  Using X-ray diffraction patterns to create the three dimensional structure they were able to see how the protein actually folds.  The Parkin protein structure is controlled by an internal regulation system, which is lost when it is affected by mutations that account for Parkinson’s disease.

When Parkin is functioning properly, it is may be able to protect the cells and lead to their longevity, and by its other roles, some of which are yet unknown, protect against the risk of Parkinson’s and other diseases.  The three dimensional crystal structure of this protein created by these young researchers is already unlocking some of the secrets of Parkin.

 

Tobias Wauer, Daid Kommander. Structure of the human Parkin ligase domain in an autoinhibited stateThe EMBO Journal, 2013: DOI: 10.1038/emboj.2013.125

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