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The dark side of amyloid: PMEL, a natural amyloid in melanosome biogenesis
A selection of talks on Biochemistry
The ERK1/2 MAPK cascade
- Prof. Melanie H. Cobb
- University of Texas Southwestern Medical Center at Dallas, USA
Amino acid conjugation: mechanism and enzymology
- Dr. Kathleen Knights
- Flinders University, Australia
Hi, my name is Mickey Marks. I'm an associate professor in the Department of Pathology and Laboratory Medicine at the University of Pennsylvania in Philadelphia. What I'd like to talk to you about today is how the amyloid fold has been exploited for use as a structural foundation of organelle biogenesis in mammalian cells.
You've heard all about from the previous lectures how the cross-beta sheet structure of amyloid generates these very stable fibrillar structures. This of course, is a big problem when amyloid is formed in the wrong place at the wrong time under pathological conditions like Alzheimer's disease and Parkinson's disease. But as one might imagine, this type of structure can also provide some function if used in the right place on the proper physiological conditions.
A good example of that, that I'm sure you've heard from the previous lectures in this series, are how certain fungi and bacteria make use of the amyloid fold. One of a good example of that is the Sup 35 prion in Saccharomyces cerevisiae, which under certain conditions forms amyloid structures that then sequester translation termination factors. This sequestration allows read-through of certain messenger RNAs to encode extra protein regions within the encoded protein, which then take on novel functions for the cell that have physiological consequences.
What I'll be talking to you about today is a different use of the amyloid fold for structural purposes, in this case, involved in organelle formation for membrane-bound organelles inside of cells. The system in which we study this is in the melanocyte, which makes an organelle called the melanosome. It's the pigment granule found in pigment cells in the eye and skin. In this case, an amyloid called Pmel17 forms a major structural foundation for the organelle that's required for its function.