Novel Insight Into Parkin Structure and Activation Elucidated by Dr. Helen Walden's Group
Dr. Helen Walden, Programme Leader of the MRC Protein Phosphorylation and Ubiquitylation Unit (MRC PPU) based at The University of Dundee, has been focused on understanding the intricate molecular architecture of proteins for over 10 years. Her group's recent finding around one particular protein – Parkin – is especially critical for the Parkinson's disease research field.
Parkinson's disease is a neurodegenerative disorder affects close to 5 million individuals worldwide, with the numbers set to increase as the population ages. Whereas the cause of Parkinson's disease is uncertain in most cases, in approximately 5% of all cases, mutations in particular genes have been identified as playing a causative role in disease development. Since 1997, close to 20 genes have been found as playing a role in PD. Parkin is a protein encoded by the PARK2 gene and manifests as an autosomal recessive form of PD with a profile of younger onset. It is thought that research on the targets encoded by these genes may lend additional insight into those who suffer from PD where there is no known genetic link.
While it is important to understand the biological ramifications of any protein, without understanding the subtle alterations that are occurring on an atomic level, it can prove difficult to fully understand the biological findings. It is this intricate task that Dr. Walden and her lab has undertaken with regard to Parkin. And in her new publication, Dr. Walden has lent keen insight into with a high-resolution structure of the whole human form of the Parkin protein – an accomplishment that has to-date eluded other investigators who have largely focused on smaller ‘pieces' of Parkin.
Past results from several laboratories around the world had demonstrated that Parkin activation relied upon two factors: 1) a special type of chemical modification called ‘phosphorylation' and interaction with another small protein called ubiquitin, that is in turn phosphorylated.
But how this occurred and how the different parts of the Parkin protein contributed to these interactions was not well delineated. Until now, that is. Dr. Walden's new findings lend insight into not only how Parkin is activated, but suggest a sequence of events that are critical to that activation.
Dr. Walden's work has far reaching implications for the pharmaceutical industry as they work towards identifying a target that may be amenable to small molecular manipulation. Parkin further represent a potential target that if successfully activated, could alter the course of progression of Parkinson's disease. This work was done jointly with Gary Shaw's Lab at the University of Western Ontario.
The final results of these studies have been published in EMBO Journal in August, 2015.
Parkinson's disease is a neurodegenerative disorder affects close to 5 million individuals worldwide, with the numbers set to increase as the population ages. Whereas the cause of Parkinson's disease is uncertain in most cases, in approximately 5% of all cases, mutations in particular genes have been identified as playing a causative role in disease development. Since 1997, close to 20 genes have been found as playing a role in PD. Parkin is a protein encoded by the PARK2 gene and manifests as an autosomal recessive form of PD with a profile of younger onset. It is thought that research on the targets encoded by these genes may lend additional insight into those who suffer from PD where there is no known genetic link.
While it is important to understand the biological ramifications of any protein, without understanding the subtle alterations that are occurring on an atomic level, it can prove difficult to fully understand the biological findings. It is this intricate task that Dr. Walden and her lab has undertaken with regard to Parkin. And in her new publication, Dr. Walden has lent keen insight into with a high-resolution structure of the whole human form of the Parkin protein – an accomplishment that has to-date eluded other investigators who have largely focused on smaller ‘pieces' of Parkin.
Past results from several laboratories around the world had demonstrated that Parkin activation relied upon two factors: 1) a special type of chemical modification called ‘phosphorylation' and interaction with another small protein called ubiquitin, that is in turn phosphorylated.
But how this occurred and how the different parts of the Parkin protein contributed to these interactions was not well delineated. Until now, that is. Dr. Walden's new findings lend insight into not only how Parkin is activated, but suggest a sequence of events that are critical to that activation.
Dr. Walden's work has far reaching implications for the pharmaceutical industry as they work towards identifying a target that may be amenable to small molecular manipulation. Parkin further represent a potential target that if successfully activated, could alter the course of progression of Parkinson's disease. This work was done jointly with Gary Shaw's Lab at the University of Western Ontario.
The final results of these studies have been published in EMBO Journal in August, 2015.