Amyloid Protein Structure: Explore Amyloids
Explore a simple introduction to protein structure, and learn about the renegade proteins (amyloid fibrils) responsible for Mad Cow and Alzheimer’s disease at The Emergent Universe, an online interactive science museum about emergence.
Explore Renegade Proteins
Or What are amyloid fibrils, anyway?
Proteins are long, ribbon-like molecules, and, as you probably know, many different proteins play important roles in our bodies. Each protein typically folds into a specific, complex structure that controls how the protein functions. In these native structures, segments of the protein chain typically form into coils, called a-helices (“alpha-helices”) (image), or into folds, called b-sheets (“beta-sheets”) (image). These segments then fold around each other in well-defined ways.
Many proteins, including those with and without known native structures, can also fold in a way that prompts them to self-aggregate into long strands called amyloid fibrils. Amyloid fibrils all share certain characteristics: they are built from stacked beta-sheets, they are extremely strong and resist degradation, and they stain like starch (hence the prefix amyl, from the Latin word for starch). Amyloid fibrils are implicated in numerous diseases, they are found in a variety of natural materials, and they are technologically promising materials.
Relevance to Emergence
Amyloid fibrils are an emergent structure because they arise from the spontaneous self-organization of many individual proteins, and this organization results from the interactions between proteins rather than from some external directive. Also, the characteristics of amyloid fibrils are largely insensitive to the underlying details of the component proteins – a robustness often associated with emergent phenomena.
More About: Protein Structure
Protein Folding - more!
Think of a protein as a molecular ribbon. Along both edges of this ribbon are hydrogens (H) and oxygens (O). The hydrogens on one edge of the ribbon are attracted to the oxygens on the other edge. It is this attraction that causes the protein to coil into alpha-helices and to fold into beta-sheets.
This ribbon structure, which forms the protein’s backbone, is the same for all proteins.
Where proteins differ from one another is in their “side chains,” small molecular groups that stick out from the flat sides of the ribbon-like backbone. It is specific interactions between these side chains that cause each protein to fold into it’s own unique native structure.
More About: Amyloid Fibrils
The common structural feature of all amyloid fibrils is called a “cross-b structure.” It involves the stacking of many proteins together, ribbon edge to ribbon edge, to create an extended beta-sheet that extends the length of the fibril. Thus, the segment of each protein’s backbone that is participating in the fibril beta-sheet lies perpendicular to the long fibril axis (image1).
image 1: the fibril grows along the axis; hydrogen-oxygen attraction holds proteins together in a beta-sheet
Recent research suggests that most amyloid fibrils are created from more than one such extended b-sheet, and different proteins form amyloid fibrils with different configurations of these extended beta-sheets, as shown below.
Fig 2. Left handed beta-helix fibril structure proposed for the mad cow protein PrPSc
Fig 3b. Side-chain-zipper fibril structure proposed for fragments of the mad cow protein PrPSc
(based on X-ray crystalography data)
(side chains on protein ribbons)
(side chains from different proteins interlock and hold the two beta-sheets together)
Fig 4. Fibril structure proposed for the Alzheimer’s Beta Amyloid protein