Polyalanine refers to a segment within a protein composed of repeating alanine units. These stretches are abundant in proteins across various eukaryotic organisms, including humans. While their precise roles are still being explored, they are recognized as a common protein component.
Amino Acids and Proteins
Understanding polyalanine requires grasping the fundamental building blocks of life: amino acids and proteins. Amino acids are small organic compounds that serve as the basic units for constructing proteins. Think of amino acids as the individual letters of an alphabet. There are 20 different types of amino acids, each with a unique chemical side chain that gives it distinct properties.
Proteins are large, complex molecules formed by linking hundreds or thousands of amino acids together in specific sequences. Just as letters combine to form words, amino acid sequences dictate the unique three-dimensional shape and function of each protein. Proteins perform a vast array of functions, acting as structural components, enzymes that drive chemical reactions, transporters of molecules, and elements of the immune system.
Understanding Polyalanine
Polyalanine refers to a continuous stretch within a protein where the amino acid alanine is repeated multiple times. This sequence can be visualized as a string of ‘A’s, such as AAAAAA. These polyalanine tracts are naturally present in a significant number of human proteins, with approximately 7.8% containing segments of four or more consecutive alanines.
In their normal state, polyalanine sequences contribute to the overall structure and stability of proteins. For instance, short polyalanine segments can form alpha-helices, common structural motifs in proteins. They can also influence how proteins interact with other molecules or help target proteins to specific locations within a cell. The length of these polyalanine tracts is typically maintained within a certain range in healthy individuals, reflecting their specific functional requirements.
Polyalanine Expansion Disorders
Polyalanine sequences can become abnormally lengthened due to specific genetic changes. These changes are typically trinucleotide repeat expansions in the DNA, meaning a small sequence of three DNA building blocks that codes for alanine is mistakenly copied too many times. This genetic error leads to the production of proteins that contain an extended, longer-than-normal polyalanine tract.
When these polyalanine tracts exceed a certain threshold length, they are associated with a group of inherited human diseases. These conditions are often neurodegenerative or muscular disorders, indicating that nerve and muscle cells are particularly affected. For example, oculopharyngeal muscular dystrophy (OPMD) is caused by an expansion in the PABPN1 gene, leading to an abnormally long polyalanine segment in the PABPN1 protein. Other conditions also arise from similar genetic expansions in different genes. The exact pathological threshold has been identified for these conditions.
How Polyalanine Expansions Harm Cells
The abnormal elongation of polyalanine tracts within proteins harms cells. When these expanded polyalanine segments are produced, they can cause the entire protein to misfold. This misfolding prevents the protein from adopting its correct three-dimensional shape, which is necessary for its proper function. Misfolded proteins have a tendency to aggregate, meaning they clump together to form insoluble deposits within cells.
These protein aggregates are toxic to cells, disrupting normal cellular processes and interfering with cellular machinery. The accumulation of these clumps can impair various cellular functions, eventually leading to cellular dysfunction and cell death. Neurons and muscle cells are particularly vulnerable to this toxicity, explaining why polyalanine expansion disorders often manifest as neurodegenerative or muscular symptoms. The progressive loss of these specialized cells underlies the observable symptoms of these inherited conditions.