3.7
Protein Complex Assembly
Most proteins do not function as fully extended polypeptide chains but assemble into compact multicomponent complexes. During assembly, the growing complex must distinguish its specific components from a mixture of hundreds of different protein and non-protein species present in the cell.
Protein complexes can be either homomeric, consisting of several copies of the same polypeptide chain, or heteromeric, composed of multiple distinct polypeptide chains or non-protein components.
Usually, proteins have all the necessary information to self-assemble into functional complexes from their constituents with speed and precision.
Many viruses can self-assemble to form a fully functional unit using the infected host cell to produce all of the necessary components.
For instance, in the tobacco mosaic virus, coat protein subunits self-assemble into individual rings, in vitro. An RNA molecule binds in the center of the growing helix to make the active virus.
However, in some protein complexes, self-assembly is only due to mutation or disease.
Hemoglobin, the oxygen-carrying protein found in red blood cells, is a tetramer of two alpha subunits and two similar beta subunits. However, in sickle cell anemia, mutant hemoglobin has a hydrophobic patch that increases the affinity between hemoglobin tetramers, causing them to aggregate into an abnormal assembly of hemoglobin fibers.
These fibers change the blood cells from a spheroid to a crescent shape, thereby clogging the blood vessels.
Although many proteins self-assemble without external help, assembly factors such as molecular chaperones assist protein components to assemble into a stable and functional complex.
The 26S proteasome, molecular machinery that assists in regulated protein degradation, consists of two distinct sub-complexes: a barrel-shaped 20S core particle and two 19S regulatory particle caps. Each sub-complex is further composed of several protein subunits.
Multiple proteasome-dedicated chaperones integrate these subunits into their respective sub-complexes. Finally, chaperones assemble the sub-complexes into the complete proteasome complex.
Proteins can form homomeric complexes with another unit of the same protein or heteromeric complexes with different types. Most protein complexes self-assemble spontaneously via ordered pathways, while some proteins need assembly factors that guide their proper assembly. Despite the crowded intracellular environment, proteins usually interact with their correct partners and form functional complexes.
Many viruses self-assemble into a fully functional unit using the infected host cell to produce all the necessary components. The tobacco mosaic virus (TMV) is a classic example of a self-assembling complex of protein subunits and RNA. The TMV self-assembly process is the basis for some of the therapeutic virus particles designed for drug delivery.
Some protein complexes self-assemble only due to mutation or disorders. Hemoglobin, the oxygen-carrying protein found in red blood cells, is a tetramer of two alpha and two beta subunits. However, in sickle cell anemia, a single point mutation replaces a hydrophilic amino acid- glutamine with a hydrophobic valine. This creates sticky hydrophobic patches on the opposite sides of the hemoglobin tetramer. In an aqueous cell environment, the hydrophobic patches on different hemoglobin molecules attach, assembling into long and rigid fibers. These fibers change the red blood cells' shape from a spheroid to a crescent shape.
Most proteins do not function as fully extended polypeptide chains but assemble into compact multicomponent complexes. During assembly, the growing complex must distinguish its specific components from a mixture of hundreds of different protein and non-protein species present in the cell.
Protein complexes can be either homomeric, consisting of several copies of the same polypeptide chain, or heteromeric, composed of multiple distinct polypeptide chains or non-protein components.
Usually, proteins have all the necessary information to self-assemble into functional complexes from their constituents with speed and precision.
Many viruses can self-assemble to form a fully functional unit using the infected host cell to produce all of the necessary components.
For instance, in the tobacco mosaic virus, coat protein subunits self-assemble into individual rings, in vitro. An RNA molecule binds in the center of the growing helix to make the active virus.
However, in some protein complexes, self-assembly is only due to mutation or disease.
Hemoglobin, the oxygen-carrying protein found in red blood cells, is a tetramer of two alpha subunits and two similar beta subunits. However, in sickle cell anemia, mutant hemoglobin has a hydrophobic patch that increases the affinity between hemoglobin tetramers, causing them to aggregate into an abnormal assembly of hemoglobin fibers.
These fibers change the blood cells from a spheroid to a crescent shape, thereby clogging the blood vessels.
Although many proteins self-assemble without external help, assembly factors such as molecular chaperones assist protein components to assemble into a stable and functional complex.
The 26S proteasome, molecular machinery that assists in regulated protein degradation, consists of two distinct sub-complexes: a barrel-shaped 20S core particle and two 19S regulatory particle caps. Each sub-complex is further composed of several protein subunits.
Multiple proteasome-dedicated chaperones integrate these subunits into their respective sub-complexes. Finally, chaperones assemble the sub-complexes into the complete proteasome complex.
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3.7 : Protein Complex Assembly
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