Concept

Dynactin

Summary
Dynactin is a 23 subunit protein complex that acts as a co-factor for the microtubule motor cytoplasmic dynein-1. It is built around a short filament of actin related protein-1 (Arp1). Dynactin was identified as an activity that allowed purified cytoplasmic dynein to move membrane vesicles along microtubules in vitro. It was shown to be a multiprotein complex and named "dynactin" because of its role in dynein activation. The main features of dynactin were visualized by quick-freeze, deep-etch, rotary shadow electron microscopy. It appears as a short filament, 37-nm in length, which resembles F-actin, plus a thinner, laterally oriented arm. Antibody labelling was used to map the location of the dynactin subunits. Dynactin consists of three major structural domains: (1) sidearm-shoulder: DCTN1/p150Glued, DCTN2/p50/dynamitin, DCTN3/p24/p22;(2)the Arp1 filament: ACTR1A/Arp1/centractin, actin, CapZ; and (3) the pointed end complex: Actr10/Arp11, DCTN4/p62, DCTN5/p25, and DCTN6/p27. A 4Å cryo-EM structure of dynactin revealed that its filament contains eight Arp1 molecules, one β-actin and one Arp11. In the pointed end complex p62/DCTN4 binds to Arp11 and β-actin and p25 and p27 bind both p62 and Arp11. At the barbed end the capping protein (CapZαβ) binds the Arp1 filament in the same way that it binds actin, although with more charge complementarity, explaining why it binds dynactin more tightly than actin. The shoulder contains two copies of p150Glued/DCTN1, four copies of p50/DCTN2 and two copies of p24/DCTN3. These proteins form long bundles of alpha helices, which wrap over each other and contact the Arp1 filament. The N-termini of p50/DCTN2 emerge from the shoulder and coat the filament, providing a mechanism for controlling the filament length. The C-termini of the p150Glued/DCTN1 dimer are embedded in the shoulder, whereas the N-terminal 1227 amino acids form the projecting arm. The arm consists of an N-terminal CAPGly domain which can bind the C-terminal tails of microtubules and the microtubule plus end binding protein EB1.
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