The Melanocytes Group of the Department of Biochemistry and Molecular Biology of the School of Medicine, University of Murcia, was established some 30 years ago bythe pioneering work of Professor José Antonio Lozano Teruel on plant polyphenol oxidases. Soon thereafter, the main research interest of the group switched to the regulation of amphibian and thenmammalian melanogenesis at the subcellular and cellular levels
The work of our team has contributed to the dramatic change in the view of the melanogenic pathway that took place from the late 80’s todate. The oversimplified picture of an atypical pathway where only a single enzyme, tyrosinase, was involved, is now replaced by the much more complex and exciting scheme shown above. The involvementof two new proteins was solidly established, and a possible role for other melanosomal proteins such as the silver locus product was also suggested.
The threeenzymatic proteins certainly involved in the pathway are known as Tyrosinase and the Tyrosinase Related Proteins (TYRPs) 1 and 2. They share most of their crucial structural features, including thepresence of a single transmembrane fragment that anchors them to the melanosomal membrane, several glycosylation and sorting signals, and, more importantly, two highly similar metal ion binding sites thatform the active site. Therefore, it is currently assumed that Tyrosinase and the TYRPS display a common overall molecular shape, such as the one depicted above for mouse Tyrosinase. In spite of thishigh similarity, the three proteins display very different enzymatic capabilities and even distinct metal ion specificity. Therefore, the Tyrosinase family provides an excellent model to studystructure-function relationships and the molecular basis of divergent evolution.
The Melanocytes Group also investigates actively the regulation of melanogenesis by...
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