Abstract
The evolutionarily conserved Arp2/3 complex plays a central role in nucleating the branched actin filament arrays that drive cell migration, endocytosis, and other processes. To better understand Arp2/3 complex regulation, we used single-particle electron microscopy to compare the structures of Arp2/3 complex bound to three different inhibitory ligands: glia maturation factor (GMF), Coronin, and Arpin. Although the three inhibitors have distinct binding sites on Arp2/3 complex, they each induced an “open” nucleation-inactive conformation. Coronin promoted a standard (previously described) open conformation of Arp2/3 complex, with the N-terminal β-propeller domain of Coronin positioned near the p35/ARPC2 subunit of Arp2/3 complex. GMF induced two distinct open conformations of Arp2/3 complex, which correlated with the two suggested binding sites for GMF. Furthermore, GMF synergized with Coronin in inhibiting actin nucleation by Arp2/3 complex. Arpin, which uses VCA-related acidic (A) motifs to interact with the Arp2/3 complex, induced the standard open conformation, and two new masses appeared at positions near Arp2 and Arp3. Furthermore, Arpin showed additive inhibitory effects on Arp2/3 complex with Coronin and GMF. Together, these data suggest that Arp2/3 complex conformation is highly polymorphic and that its activities can be controlled combinatorially by different inhibitory ligands.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 237-248 |
| Number of pages | 12 |
| Journal | Journal of Molecular Biology |
| Volume | 429 |
| Issue number | 2 |
| DOIs | |
| State | Published - Jan 20 2017 |
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Keywords
- actin nucleation
- conformation
- single-particle EM
- yeast
ASJC Scopus subject areas
- Molecular Biology
Cite this
Structural Basis of Arp2/3 Complex Inhibition by GMF, Coronin, and Arpin. / Sokolova, Olga S.; Chemeris, Angelina; Guo, Siyang; Alioto, Salvatore L.; Gandhi, Meghal; Padrick, Shae; Pechnikova, Evgeniya; David, Violaine; Gautreau, Alexis; Goode, Bruce L.
In: Journal of Molecular Biology, Vol. 429, No. 2, 20.01.2017, p. 237-248.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Structural Basis of Arp2/3 Complex Inhibition by GMF, Coronin, and Arpin
AU - Sokolova, Olga S.
AU - Chemeris, Angelina
AU - Guo, Siyang
AU - Alioto, Salvatore L.
AU - Gandhi, Meghal
AU - Padrick, Shae
AU - Pechnikova, Evgeniya
AU - David, Violaine
AU - Gautreau, Alexis
AU - Goode, Bruce L.
PY - 2017/1/20
Y1 - 2017/1/20
N2 - The evolutionarily conserved Arp2/3 complex plays a central role in nucleating the branched actin filament arrays that drive cell migration, endocytosis, and other processes. To better understand Arp2/3 complex regulation, we used single-particle electron microscopy to compare the structures of Arp2/3 complex bound to three different inhibitory ligands: glia maturation factor (GMF), Coronin, and Arpin. Although the three inhibitors have distinct binding sites on Arp2/3 complex, they each induced an “open” nucleation-inactive conformation. Coronin promoted a standard (previously described) open conformation of Arp2/3 complex, with the N-terminal β-propeller domain of Coronin positioned near the p35/ARPC2 subunit of Arp2/3 complex. GMF induced two distinct open conformations of Arp2/3 complex, which correlated with the two suggested binding sites for GMF. Furthermore, GMF synergized with Coronin in inhibiting actin nucleation by Arp2/3 complex. Arpin, which uses VCA-related acidic (A) motifs to interact with the Arp2/3 complex, induced the standard open conformation, and two new masses appeared at positions near Arp2 and Arp3. Furthermore, Arpin showed additive inhibitory effects on Arp2/3 complex with Coronin and GMF. Together, these data suggest that Arp2/3 complex conformation is highly polymorphic and that its activities can be controlled combinatorially by different inhibitory ligands.
AB - The evolutionarily conserved Arp2/3 complex plays a central role in nucleating the branched actin filament arrays that drive cell migration, endocytosis, and other processes. To better understand Arp2/3 complex regulation, we used single-particle electron microscopy to compare the structures of Arp2/3 complex bound to three different inhibitory ligands: glia maturation factor (GMF), Coronin, and Arpin. Although the three inhibitors have distinct binding sites on Arp2/3 complex, they each induced an “open” nucleation-inactive conformation. Coronin promoted a standard (previously described) open conformation of Arp2/3 complex, with the N-terminal β-propeller domain of Coronin positioned near the p35/ARPC2 subunit of Arp2/3 complex. GMF induced two distinct open conformations of Arp2/3 complex, which correlated with the two suggested binding sites for GMF. Furthermore, GMF synergized with Coronin in inhibiting actin nucleation by Arp2/3 complex. Arpin, which uses VCA-related acidic (A) motifs to interact with the Arp2/3 complex, induced the standard open conformation, and two new masses appeared at positions near Arp2 and Arp3. Furthermore, Arpin showed additive inhibitory effects on Arp2/3 complex with Coronin and GMF. Together, these data suggest that Arp2/3 complex conformation is highly polymorphic and that its activities can be controlled combinatorially by different inhibitory ligands.
KW - actin nucleation
KW - conformation
KW - single-particle EM
KW - yeast
UR - http://www.scopus.com/inward/record.url?scp=85008230376&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85008230376&partnerID=8YFLogxK
U2 - 10.1016/j.jmb.2016.11.030
DO - 10.1016/j.jmb.2016.11.030
M3 - Article
C2 - 27939292
AN - SCOPUS:85008230376
VL - 429
SP - 237
EP - 248
JO - Journal of Molecular Biology
JF - Journal of Molecular Biology
SN - 0022-2836
IS - 2
ER -