PubMed Health⌕ Search
Home/Archive/PubMed

PubMed · 11721045

Crystal structure of Arp2/3 complex.

R C Robinson·K Turbedsky·D A Kaiser·J B Marchand·H N Higgs·S Choe·T D Pollard
View original source ↗Export metadata ↓

Abstract

We determined a crystal structure of bovine Arp2/3 complex, an assembly of seven proteins that initiates actin polymerization in eukaryotic cells, at 2.0 angstrom resolution. Actin-related protein 2 (Arp2) and Arp3 are folded like actin, with distinctive surface features. Subunits ARPC2 p34 and ARPC4 p20 in the core of the complex associate through long carboxyl-terminal alpha helices and have similarly folded amino-terminal alpha/beta domains. ARPC1 p40 is a seven-blade beta propeller with an insertion that may associate with the side of an actin filament. ARPC3 p21 and ARPC5 p16 are globular alpha-helical subunits. We predict that WASp/Scar proteins activate Arp2/3 complex by bringing Arp2 into proximity with Arp3 for nucleation of a branch on the side of a preexisting actin filament.

Explore related subjects

Actin CytoskeletonActin-Related Protein 2Actin-Related Protein 3ActinsAdenosine TriphosphateAnimalsCattleCrystallography, X-RayCytoskeletal ProteinsMacromolecular SubstancesModels, BiologicalModels, MolecularMuscle, SkeletalProtein Structure, QuaternaryProtein Structure, SecondaryProtein Structure, TertiaryProtein SubunitsStatic ElectricityThymus GlandJournal ArticleResearch Support, Non-U.S. Gov'tResearch Support, U.S. Gov't, P.H.S.

Keep this discovery

Explore connections, maps & timelines

BibTeXRIS

R C Robinson, K Turbedsky, D A Kaiser, J B Marchand, H N Higgs, S Choe, T D Pollard. 2001-11-23. Crystal structure of Arp2/3 complex.. https://doi.org/10.1126/science.1066333

Cite the original work for its findings. Save a collection to share your selection of sources.

KEEP EXPLORING

Related citations

PubMed2022

Heterozygous Tropomodulin 3 mice have improved lung vascularization after chronic hypoxia.

The molecular mechanisms leading to high-altitude pulmonary hypertension (HAPH) remains poorly understood. We previously analyzed the whole genome sequence of Kyrgyz highland population and identified eight genomic intervals having a potential role in HAPH. Tropomodulin 3 gene (TMOD3), which encodes a protein that binds and caps the pointed ends of actin filaments and inhibits cell migration, was one of the top candidates. Here we systematically sought additional evidence to validate the functional role of TMOD3. In-silico analysis reveals that some of the SNPs in HAPH associated genomic intervals were positioned in a regulatory region that could result in alternative splicing of TMOD3. In order to functionally validate the role of TMOD3 in HAPH, we exposed Tmod3-/+ mice to 4&#xa0;weeks of constant hypoxia, i.e. 10% O2 and analyzed both functional (hemodynamic measurements) and structural (angiography) parameters related to HAPH. The hemodynamic measurements, such as right ventricular systolic pressure, a surrogate measure for pulmonary arterial systolic pressure, and right ventricular contractility (RV-&#x2009;&#xb1;&#x2009;dP/dt), increases with hypoxia did not separate between Tmod3-/+ and control mice. Remarkably, there was a significant increase in the number of lung vascular branches and total length of pulmonary vascular branches (P&#x2009;<&#x2009;0.001) in Tmod3-/+ after 4&#xa0;weeks of constant hypoxia as compared with controls. Notably, the Tmod3-/+ endothelial cells migration was also significantly higher than that from the wild-type littermates. Our results indicate that, under chronic hypoxia, lower levels of Tmod3 play an important role in the maintenance or neo-vascularization of pulmonary arteries.

Actin Cytoskeleton↗
PubMed2007

Dynamics of bidirectional transport of Arc mRNA in neuronal dendrites.

The mRNA for Arc (activity-regulated cytoskeletal protein) is delivered into dendrites and localizes selectively at active synapses. Here we use a green fluorescent protein-based labeling system and confocal microscopy to define the transport kinetics of exogenously expressed mRNA from chimaeric Arc constructs (Arc/MS2 mRNA) in the dendrites of living rat neurons in culture. Arc/MS2 mRNA assembles into particles that move independently, bidirectionally, and intermittently in a fashion indicative of transport. Transport velocities range from below 6 to 65 mum/minute, which is consistent with actin-based and microtubule-based transport, respectively. In general, orthograde translocations are longer than retrograde translocations. Rapidly translocating Arc/MS2 mRNA particles sometimes reverse direction and decrease velocity just before stopping, suggesting that local signals regulate Arc mRNA targeting movements. These observations identify several phases of Arc mRNA movement that serve as potential points for regulating Arc mRNA localization.

Actin Cytoskeleton↗
PubMed2007

Actin polymerization under pressure: a theoretical study.

An extended Flory-Huggins-type equilibrium polymerization theory for compressible systems is used to describe experimental data for the unusual pressure and temperature dependence of the equilibrium polymerization of G-actin to F-actin. The calculations provide rich insights into the reaction mechanism and the thermodynamics of actin polymerization at the molecular level. Volume changes associated with individual steps of the mechanism are calculated to be DeltaVactiv=(s1*-s1)upsilon0=+1553 mlmol for the activation reaction, DeltaVdim=(s2-s1*)upsilon0=-3810 mlmol for dimerization, and DeltaVprop=(sP-s1)upsilon0=+361 mlmol for the propagation reaction, where s1upsilon0, s1*upsilon0, s2upsilon0, and sPupsilon0 are the monomer volumes in the G-actin monomer, the activated G-action, the dimer, and higher polymers, respectively. Comparison with experimental measurements is made, and discrepancies are discussed.

Actin Cytoskeleton↗