Actin is a protein found in nearly all eukaryotic cells and is a primary component of the cytoskeleton, a network of fibers providing structural support and shape. The protein’s ability to change its structure is fundamental to cellular processes like movement, division, and internal transport. This dynamic nature allows actin to assemble and disassemble into various configurations, enabling cells to adapt to their environment.
The Monomeric Form (G-Actin)
The basic building block of actin structures is a single, soluble protein called globular actin, or G-actin. Weighing approximately 42 kDa, this monomer has a distinct, roughly spherical shape. The structure is organized into two main lobes, which create a deep cleft in the center that serves as a binding site for adenosine triphosphate (ATP) or adenosine diphosphate (ADP), along with a magnesium ion.
The presence of a bound ATP or ADP molecule is necessary to stabilize the G-actin monomer and prevent it from denaturing. The binding and subsequent hydrolysis of ATP to ADP releases energy that drives conformational changes in the actin protein. This energy transaction is a preparatory step for assembling G-actin into filaments, where the nucleotide’s state affects filament stability and dynamics.
Filamentous Assembly (F-Actin)
Individual G-actin units polymerize to form long chains known as filamentous actin, or F-actin. These filaments are a major component of the cell’s cytoskeleton. During polymerization, two chains, called protofilaments, wind around each other in a right-handed double helix. This helical structure gives the filament both strength and flexibility, with a diameter of about 7 nm.
A defining feature of F-actin is its structural polarity, meaning the two ends of the filament are different. This arises because every G-actin monomer is asymmetrical and orients itself in the same direction during polymerization. This uniform orientation creates a “plus” end, also called the barbed end, and a “minus” end, known as the pointed end.
This structural polarity has direct functional consequences for the filament’s growth. The rate of G-actin addition is significantly faster at the plus end compared to the minus end. Cells exploit this difference to control the direction of filament growth for processes like cell migration. The polarity ensures that actin-based structures can be built and remodeled in a controlled manner.
Dynamic Nature of Actin Filaments
Actin filaments are not static structures but exist in a state of continuous flux, a phenomenon known as treadmilling. This process allows a filament to maintain a relatively constant length while individual actin subunits are in motion. Treadmilling occurs when the net rate of G-actin monomer addition at the plus end matches the net rate of monomer removal from the minus end.
This dynamic behavior is linked to the ATP hydrolysis that occurs after a G-actin monomer is incorporated into the filament. G-actin, bound to ATP, adds to the growing plus end. Over time, this ATP is hydrolyzed to ADP, and the phosphate is released, leaving ADP-bound actin in the filament. ADP-actin has a weaker affinity for its neighbors, which destabilizes the filament and promotes subunit dissociation from the minus end.
The entire cycle of ATP-actin addition, hydrolysis, and ADP-actin dissociation powers the treadmilling process. This constant turnover enables the cell to rapidly reorganize its actin cytoskeleton. For example, in a migrating cell, existing filaments can be disassembled at the rear, freeing G-actin monomers to be transported to the leading edge to build new filaments, driving the cell forward.
Regulation by Actin-Binding Proteins
The dynamics of actin are controlled by a diverse group of over 100 actin-binding proteins (ABPs). These proteins interact with G-actin or F-actin to modify nearly every aspect of filament behavior, from formation to organization. Cells use ABPs to tailor the actin cytoskeleton for specific tasks, ensuring the right structures are built at the right time and place.
Some ABPs initiate the formation of new filaments, a process known as nucleation. The Arp2/3 complex, for example, binds to the side of an existing filament and creates a new branch, forming a web-like network. Other proteins, like formins, promote the creation of long, unbranched filaments. Severing proteins such as cofilin break F-actin into smaller pieces, increasing the number of ends and accelerating disassembly.
Other ABPs control filament length and stability. Capping proteins, like CapZ, bind to the plus ends of filaments, preventing both the addition and loss of subunits, which stabilizes the filament. To create more complex structures, cross-linking proteins like filamin and fimbrin organize filaments into bundles or networks. Filamin forms flexible cross-links for gel-like networks, while fimbrin creates tightly packed, parallel bundles.