Protein fusion combines two or more distinct proteins into a single, new protein. This process can occur naturally or be engineered in a laboratory. The resulting fused protein often exhibits combined or enhanced functions from its original components, making it valuable in scientific and medical fields.
What Are Fusion Proteins?
Fusion proteins are hybrid molecules created by joining the genetic instructions for two or more separate proteins. This engineered or natural combination results in a single, continuous polypeptide chain during protein synthesis. A fusion protein often includes a “tag” for laboratory processes and a “target” protein whose function is being investigated.
The original proteins’ individual functions can be preserved, modified, or enhanced within the new fusion protein. For example, combining a protein that binds to a specific target with an enzymatic protein creates a molecule with both targeting and catalytic abilities. These combined functionalities enable fusion proteins to perform complex tasks beyond individual proteins. A short peptide sequence, called a linker, is sometimes inserted between fused segments to ensure proper folding and function.
How Are Fusion Proteins Engineered?
Scientists create fusion proteins in the laboratory using recombinant DNA technology. This process starts by identifying and isolating the specific DNA sequences, or genes, that code for the proteins to be fused. These gene segments are then precisely joined, often by removing the stop codon from the first gene and attaching the second gene in-frame.
Once linked, this new fusion gene is inserted into a “vector,” typically a plasmid or sometimes a virus. This vector delivers the fusion gene into a host organism, such as bacteria, yeast, or mammalian cells. The host cell’s machinery then reads these genetic instructions, transcribing the fusion gene into messenger RNA and translating it into a single, continuous fusion protein. This enables large-scale production and purification of the engineered fusion protein.
Applications Across Science and Medicine
Engineered fusion proteins have broad applications in scientific research, diagnostics, and therapeutics. In research, they are used as tools for protein purification. An “affinity tag” like a His-tag is fused to a target protein, allowing it to bind specifically to a purification column. These tags also help detect proteins in complex mixtures and study protein interactions.
In diagnostics, fusion proteins serve as valuable reagents or detection markers. They can be designed to bind to specific disease markers, enabling identification in patient samples. This supports the development of sensitive diagnostic tests.
In therapeutics, fusion proteins are designed to act as drugs. One strategy combines an antibody fragment for precise cell targeting with a therapeutic protein that delivers a desired action, such as inducing cell death in cancer cells. Another application creates long-acting protein drugs by fusing a therapeutic protein to an antibody fragment that extends its half-life, reducing dosing frequency.
Natural Fusion Proteins and Their Significance
While many fusion proteins are engineered, some occur naturally within living organisms. The most recognized natural occurrences result from chromosomal translocations, particularly in certain cancers. These translocations involve the abnormal joining of segments from two different chromosomes, leading to the fusion of two previously separate genes.
When expressed, these fused genes create novel fusion proteins that can drive cancer development and progression. A well-known example is the BCR-ABL fusion protein, a hallmark of chronic myeloid leukemia. This abnormal protein acts as a constitutively active kinase, promoting uncontrolled cell growth. Understanding these natural fusion proteins allows researchers to develop targeted therapies that inhibit their activity, offering a precise approach to cancer treatment.