The actin protein exists in two major forms in the cell: as individual molecules
of globular (G)-actin, or linked together as long filaments of fibrous (F)-actin.
Actin microfilaments provide the primary scaffolding for contractile muscle
fibers, and act as a key component of cellular infrastructure in general. However,
many cell types also derive their mobility from directional microfilament growth
and disassembly, a process powered in part by the hydrolysis of energy-providing
adenosine triphosphate (ATP) molecules.
 | | Overview of the actin assembly/disassembly process. G-actin (top right) is bound by ATP (top right) and undergoes a transition into the F-state, enabling it to assemble into fibers (bottom left). This transition involves rotation of the two major domains into a ’flattened’ state (bottom right). This shift also enables ATP hydrolysis (top left), subsequently driving subunit dissociation and a return to G-actin conformation.
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Although crude structural data on actin have been available for well over a
decade, these have proven insufficient to provide a detailed understanding of
the mechanism of the G-to-F-actin transition and ATP binding and hydrolysis.
As such, a high-resolution structure of F-actin published recently in Nature
by RIKEN SPring-8
Center researcher Toshiro Oda and his colleagues represents an important leap
forward in understanding the function of this essential protein*.
Their findings revealed a major structural difference between the two states,
an overall ‘flattening’ of the actin molecule as it enters the F
state, brought about by a large shift in the relative positioning of the protein’s
two segments. “A simple rotation of the two major domains of the actin
molecule is the essence of the G- to F-actin transition,” explains Oda.
“This simple rotation produces the flat conformation.”
In the current model for microfilament assembly, the association of ATP with
F-actin has a stabilizing effect, while the hydrolysis of ATP by actin’s
enzymatic subdomain is believed to destabilize the F-actin and induce localized
disruption of the microfilament. The data from Oda’s team indicate that
the flattening of F-actin not only drives fiber polymerization, but also leads
to other internal rearrangements favorable to subsequent ATP hydrolysis, although
additional analysis will be required to confirm this.
*Oda, T., Iwasa, M., Aihara, T., Maeda, Y. & Narita, A. The nature of the
globular- to fibrous-actin transition. Nature 457, 441–445 (2009).
Posted April 23rd, 2009
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