The Arp-Subunits and Actin: Similarities and Differences

The two Actin-related proteins, 2 and 3 respectively, show significant homology with actin which also has implications for the mode of action of these two subunits within the process of actin nucleation and branch formation. Sequence- and structural comparison with beta-actin could provide us with valuable information regarding the mechanism of action of Arp2 and Arp3 respectively.

Multiple sequence alignments comparing bovine beta-actin to both Arp2 and Arp3 aids identification of important residues and domains within the Arp-subunits which play a role in the nucleation process. Used for the comparison is a X-ray 2.55 A-resolution crystalline structure of bovine profilin-beta-actin provided by Schutt et al. [7]. Profilin-bound active is the major component of the unpolymerized actin monomer ‘pool’ of which subunits are recruited once the Arp2/3-complex (and a set of other essential proteins) is activated and branch formation occurs [8].

The most striking similarity is the conserved ATP-binding domains present in both beta-actin and Arp2; Arp2 contains one single insertion loop not present in beta-actin, while Arp3 possesses four insertion loops and does not share any of the ATP-binding domains with beta-actin; although Arp3 is known to bind nucleotides, which causes significant conformational changes that propagate throughout the complex, very little hydrolysis-activity was observed. The insertion loops of Arp3 are predicted to be solvent-exposed surface loops. Although there is some residue-conservation in regions of inter-subunit contacts, neither Arp2 nor Arp3 is found to be capable of assembling in filaments with actin, but possibly the two Arps could contact each other to mimic an actin dimer [9], providing the basis for the suggestion that the two Arp-subunits possibly provide the first two subunits of a new branch.

Figure 4. Bovine profilin-bound beta-actin (blue), modelled with ATP-molecule (red ‘stick’-model) and ATP-binding sites (found through Multiple Sequence Alignment) indicated.

Figure 4. Bovine profilin-bound beta-actin (blue), modelled with ATP-molecule (red ‘stick’-model) and ATP-binding sites (found through Multiple Sequence Alignment) indicated.

Figure 6. Bovine Arp3-subunit singled out, with insertion loops (indicated by Multiple Sequence Alignment with bovine beta-actin) indicated in ‘hot pink’.

Figure 6. Bovine Arp3-subunit singled out, with insertion loops (indicated by Multiple Sequence Alignment with bovine beta-actin) indicated in ‘hot pink’.

 

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