10 research outputs found
Small Molecules CK-666 and CK-869 Inhibit Actin-Related Protein 2/3 Complex by Blocking an Activating Conformational Change
Get PDFSummaryActin-related protein 2/3 (Arp2/3) complex is a seven-subunit assembly that nucleates branched actin filaments. Small molecule inhibitors CK-666 and CK-869 bind to Arp2/3 complex and inhibit nucleation, but their modes of action are unknown. Here, we use biochemical and structural methods to determine the mechanism of each inhibitor. Our data indicate that CK-666 stabilizes the inactive state of the complex, blocking movement of the Arp2 and Arp3 subunits into the activated filament-like (short pitch) conformation, while CK-869 binds to a serendipitous pocket on Arp3 and allosterically destabilizes the short pitch Arp3-Arp2 interface. These results provide key insights into the relationship between conformation and activity in Arp2/3 complex and will be critical for interpreting the influence of the inhibitors on actin filament networks inĀ vivo
Human Ska complex and Ndc80 complex interact to form a load-bearing assembly that strengthens kinetochoreāmicrotubule attachments
No full textDip1 Co-opts Features of Branching Nucleation to Create Linear Actin Filaments that Activate WASP-Bound Arp2/3 Complex
No full textCrystallization and preliminary X-ray analysis of Ebola VP35 interferon inhibitory domain mutant proteins
No full textThree mutant forms of Ebola VP35 interferon inhibitory domain were crystallized in three different space groups
Interactions with Actin Monomers, Actin Filaments, and Arp2/3 Complex Define the Roles of WASP Family Proteins and Cortactin in Coordinately Regulating Branched Actin Networks
No full textSingle-Turnover Activation of Arp2/3 Complex by Dip1 May Balance Nucleation of Linear versus Branched Actin Filaments
No full textSmall Molecules CK-666 and CK-869 Inhibit Actin-Related Protein 2/3 Complex by Blocking an Activating Conformational Change
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