Actin trimer

The leucine zipper DNA-binding proteins, described in Chapter 10, are examples of globular proteins that use coiled coils to form both homo- and heterodimers. A variety of fibrous proteins also have heptad repeats in their sequences and use coiled coils to form oligomers, mainly dimers and trimers. Among these are myosin, fibrinogen, actin cross-linking proteins such as spectrin and dystrophin as well as the intermediate filament proteins keratin, vimentin, desmin, and neurofilament proteins. 

True self-assembly is observed in the formation of many oligomeric proteins. Indeed, Friedman and Beychok reviewed efforts to define the subunit assembly and reconstitution pathways in multisubunit proteins, and all of the several dozen examples cited in their review represent true self-assembly. Polymeric species are also formed by true self-assembly, and the G-actin to F-actin transition is an excellent example. By contrast, there are strong indications that ribosomal RNA species play a central role in specifying the pathway to and the structure of ribosome particles. And it is interesting to note that the assembly of the tobacco mosaic virus (TMV) appears to be a two-step hybrid mechanism the coat protein subunits first combine to form 34-subunit disks by true self-assembly from monomeric and trimeric com-... 

Figure 5.13. Assembly of actin filaments. The diagram shows the steps in the transition of actin monomer, G-actin, to actin filaments, F-actin. Monomers are activated by binding calcium and then exchanging calcium for magnesium, leading to nucleus formation. The nucleus consists of a trimer of G-actin with one pointed end and one barbed end. The addition of activated G-actin monomer to the nucleus causes elongation of the barbed end faster than the pointed end.

Gatficld J, Albrecht I, Zanolari B et al. Association of the leukocyte plasma membrane with the actin cyto-skeleton through coiled coil-mediated trimeric coronin 1 molecules. Mol Biol Cell 2005 16 2786-98. 

The simplest case of nucieation is for actin, where many studies have shown that even under polymerizing conditions, the affinity of actin monomers for each other is very low, but that when trimers or larger oligomers form, they are stable and act as the seed onto which additional monomers can add. Since the stmcture of the actin monomer is asymmetric, and since monomers bind each other head-to-tail (as well as side-to-side), the nuclei for polymerization are also asymmetric, leading to a polarity in the filament (see Figure 3). By convention, based on the stmcture of an F-actin complex with a myosin fragment that gives the filaments an arrowhead appearance, one end of the filament is called the barbed end and the other the pointed end. As discussed below, these two ends are not only stmcturally distinct but the kinetics and affinity with which monomers add to these ends are also different. 

Figure 6 Scheme for the polymerization of actin-ADP. Two dimers (ccf and ab bonds) originate identicai trimers that may elongate by addition of unimers at either end through the simultaneous formation of aband cd bonds. A steady-state situation Is eventually reached with each end independently at equilibrium with unimers. (From E.D. Korn. Physiol. Rev. 62 672,1982. With permission.)... 

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