Arp2/3 complex

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Atomic structure of bovine Arp2/3 complex (PDB code: 1k8k).[1] Color coding for subunits: Arp3, orange; Arp2, marine (subunits 1 & 2 not resolved and thus not shown); p40, green; p34, ice blue; p20, dark blue; p21, magenta; p16, yellow.

Arp2/3 complex (Actin Related Protein 2/3 complex) is a seven-subunit

eukaryotic cells.[2]
Two of its subunits, the Actin-Related Proteins ARP2 and ARP3, closely resemble the structure of monomeric actin and serve as nucleation sites for new actin filaments. The complex binds to the sides of existing ("mother") filaments and initiates growth of a new ("daughter") filament at a distinctive 70 degree angle from the mother. Branched actin networks are created as a result of this nucleation of new filaments. The regulation of rearrangements of the actin cytoskeleton is important for processes like cell locomotion,
vesicles
.

The Arp2/3 complex was named after it was identified in 1994 by affinity chromatography from

plants.[2]

Mechanisms of actin polymerization by Arp2/3

Side branching model of the Arp2/3 complex. Activated Arp2/3 complex binds to the side of a "mother" actin filament. Both Arp2 and Arp3 form the first two subunits in the new "daughter" filament.
Barbed end branching model of the Arp2/3 complex. Activated Arp2/3 competes with capping proteins to bind to the barbed end of an actin filament. Arp2 remains bound to the mother filament, while Arp3 is outside. The two Arp subunits form the first subunits of each branch and the two branches continue to grow by addition of G-actin to each Arp

Many actin-related molecules create a free barbed end for

Wiskott-Aldrich syndrome family protein (WASP, N-WASP, WAVE, and WASH proteins). The V domain of a WASP protein interacts with actin monomers while the CA region associates with the Arp2/3 complex to create a nucleation core. However, de novo nucleation followed by polymerization is not sufficient to form integrated actin networks, since these newly synthesized polymers would not be associated with pre-existing filaments. Thus, the Arp2/3 complex binds to pre-existing filaments so that the new filaments can grow on the old ones and form a functional actin cytoskeleton.[5] Capping proteins limit actin polymerization to the region activated by the Arp2/3 complex, and the elongated filament ends are recapped to prevent depolymerization and thus conserve the actin filament.[6]

The Arp2/3 complex simultaneously controls nucleation of actin polymerization and branching of filaments. Moreover, autocatalysis is observed during Arp2/3-mediated actin polymerization. In this process, the newly formed filaments activate other Arp2/3 complexes, facilitating the formation of branched filaments.

The mechanism of actin filament initiation by Arp2/3 has been disputed. The question is where the complex binds the filament and nucleates a "daughter" filament. Historically two models have been proposed. Recent results favour the side branching model, in which the Arp2/3 complex binds to the side of a pre-existing ("mother") filament at a point different from the nucleation site. Although the field lacks a high-resolution crystal structure, data from electron microscopy,[7][8][9] together with biochemical data on the filament nucleation and capping mechanisms of the Arp2/3 complex,[10] favour side branching. In the alternative barbed end branching model, Arp2/3 only associates at the barbed end of growing filaments, allowing for the elongation of the original filament and the formation of a branched filament.,[11] a model based on kinetic analysis and optical microscopy.

Recent computer docking, independently confirmed by EM data, favors a side-branching model. ARPC2 and ARPC4 together form an area that attach the base of the branch to the side of a mother filament.[12] Large conformational changes occur on nucleotide and WASP binding.[9][13]

Cellular uses of Arp2/3

The Arp2/3 complex appears to be important in a variety of specialized cell functions that involve the actin cytoskeleton. The complex is found in cellular regions characterized by dynamic actin filament activity: in macropinocytic cups, in the leading edge of motile cells (

vesicles, and mitochondria.[20] Moreover, recent studies show that the Arp2/3 complex is essential for proper polar cell expansion in plants. Arp2/3 mutations in Arabidopsis thaliana result in abnormal filament organization, which in turn affects the expansion of trichomes, pavement cells, hypocotyl cells, and root hair cells.[21][22] Chemical inhibition or genetic mutation of the Chlamydomonas reinhardtii Arp2/3 complex decreases the length of flagella.[23][24]

Subunits

The Arp2/3 complex is composed of seven subunits: Arp2/ACTR2, Arp3/ACTR3, p41/ARPC1A&B/Arc40/Sop2/p40, p34/ARPC2/ARC35/p35, p21/ARPC3/ARC18/p19, p20/ARPC4/ARC19/p18, p16/ARPC5/ARC15/p14.[25][26] The subunits Arp2 and Arp3 closely resemble monomeric actin allowing for a thermodynamically stable actin-like dimer. p41 has been proposed to interact with nucleation promoting factors (NPFs) because it is only known to have minor contacts with the mother filament and there is a major loss of nucleation efficiency in the absence of p41. p34 and p20 dimerize to form a structural backbone that mediates the interaction with the mother filament. p21 forms a bridge between Arp3 and the mother filament, increasing nucleation efficiency. p16 tethers Arp2 to the rest of the complex.[27]

References

  1. S2CID 18088124
    .
  2. ^
    PMID 20573979
    .
  3. PMID 7929556
    .
  4. PMID 2512303
    .
  5. PMID 17477841
    .
  6. PMID 15741975
    .
  7. PMID 16262445
    .
  8. S2CID 17427295
    .
  9. ^
    PMID 18316411
    .
  10. PMID 15094799
    .
  11. S2CID 28209883
    .
  12. PMID 20404198
    .
  13. PMID 21676863
    .
  14. PMID 11950888
    .
  15. S2CID 33742268
    .
  16. PMID 11807934
    .
  17. PMID 12589062
    .
  18. PMID 21874009
    .
  19. S2CID 44343534
    .
  20. S2CID 423293
    .
  21. PMID 16181803
    .
  22. S2CID 23098801
    .
  23. PMID 25155506
    .
  24. S2CID 233178920
    .
  25. S2CID 20645116
    .
  26. PMID 27595492
    .
  27. PMID 27595492
    .

External links

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