My various thoughts on actin

Oosawa, Fumio

doi:10.2142/biophysico.15.0_151

Cited by 4 publications

(3 citation statements)

References 40 publications

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“…Gactin has been well characterized structurally and several crystal structures are available (Mouilleron et al, 2012 ;Kotila et al, 2018). Over the years, there has been a gradual increase in both crystal (Holmes et al, 1990;Oda et al, 2009;von der Ecken et al, 2014) and cryo-EM (Fujii et al, 2010;Galkin et al, 2010Galkin et al, , 2015 structural data on F-actin with increasing resolution (Oosawa, 2018). Quite recently, the cryo-EM structures of an actin filament in complex with myosin VI (Gurel et al, 2017) and cofilin (Tanaka et al, 2018) were resolved.…”

Section: Structural Dynamics Of the Actin Cytoskeletonmentioning

confidence: 99%

Actin Cytoskeleton and Membrane Interactions: Role in GPCR Function and Organization

Prakash

Sengupta²,

Krishna³

2019

PINSA

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Cell signaling networks are generally initiated at the cell membrane and mediated by receptors such as the G proteincoupled receptors (GPCRs). Adjacent to the cell membrane lies a complex network of proteins-the actin cytoskeleton to which several structural and physiological roles have been attributed. An emerging role of the cytoskeleton is to modulate GPCR function and organization, either directly or indirectly. The GPCR-cytoskeleton cross-talk is a complex hierarchical process where each step has its own set of rules and combinations. Due to the inherent complexity involved at each step and the multiple spatio-temporal levels, a complete picture is yet to emerge. In this review article, we provide an overview of actin-membrane interactions and how they modulate GPCR function and organization. In this context, we briefly discuss the structural characterization of actin monomers and filaments together with their interactions with partner proteins, such as the actin binding proteins. The effect of actin interactions on membrane domains is examined that assumes significance in light of membrane modulated effects in GPCR function. We aim to bring together concepts in GPCR signaling and cytoskeletal dynamics towards addressing emerging concepts in GPCR function.

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Section: Structural Dynamics Of the Actin Cytoskeletonmentioning

confidence: 99%

Actin Cytoskeleton and Membrane Interactions: Role in GPCR Function and Organization

Prakash

Sengupta²,

Krishna³

2019

PINSA

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“…In this study, therefore, we investigated actin genes, one of the highly conserved gene families and tried to find a way for improvement of the prediction. Actin genes and proteins have been studied in numerous aspects [16][17][18][19][20]. Actin protein is an ATPase enzyme, but it mainly works as a structural protein.…”

Section: Introductionmentioning

confidence: 99%

Computational study of the impact of nucleotide variations on highly conserved proteins: In the case of actin

et al. 2022

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Edited by Haruki NakamuraSequencing of individual human genomes enables studying relationship among nucleotide variations, amino acid substitutions, effect on protein structures and diseases. Many studies have found general tendencies, for instance, that pathogenic variations tend to be found in the buried regions of the protein structures, that benign variations tend to be found on the surface of the proteins, and that variations on evolutionary conserved residues tend to be pathogenic. These tendencies were deduced from globular proteins with standard evolutionary changes in amino acid sequences. In this study, we investigated the variation distribution on actin, one of the highly conserved proteins. Many nucleotide variations and three-dimensional structures of actin have been registered in databases. By combining those data, we found that variations buried inside the protein were rather benign and variations on the surface of the protein were pathogenic. This idiosyncratic distribution of the variation impact is likely ascribed to the extensive use of the surface of the protein for protein-protein interactions in actin.

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“…The polymerization of actin proteins into filaments is of fundamental importance in basic cellular functions such as cell migration, cytokinesis, and neuron growth (1). A long history of thermodynamic, kinetic and structural studies of actin established that conversion of actin monomers (G-actin) into filaments (F-actin) involves the creation of a nucleus of 3-4 subunits that grows by polymerization above a critical monomer concentration ∼ 0.1 µM (under typical polymerization buffer conditions) (2)(3)(4). The free energy of hydrolysis of monomer-bound ATP, which occurs following polymerization and associated with a conformational change of the actin molecule from G to F form, maintains a treadmilling steady state with net polymerization (depolymerization) at the barbed (pointed) end, even in the absence of cellular co-factors that further accelerate turnover by several times in cells (3,5,6).…”

Section: Introductionmentioning

confidence: 99%

Insights into Actin Polymerization and Nucleation Using a Coarse-Grained Model

Horan

Hall

Vavylonis

2020

Biophysical Journal

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We studied actin filament polymerization and nucleation with molecular dynamics simulations and a previously established coarse-grained model having each residue represented by a single interaction site located at the C α atom. We approximate each actin protein as a fully or partially rigid unit to identify the equilibrium structural ensemble of interprotein complexes. Monomers in the F-actin configuration bound to both barbed and pointed ends of a short F-actin filament at the anticipated locations for polymerization. Binding at both ends occurred with similar affinity. Contacts between residues of the incoming subunit and the short filament were consistent with expectation from models based on crystallography, X-ray diffraction and cryo-electron microscopy. Binding at the barbed and pointed end also occurred at an angle with respect to the polymerizable bound structure, and the angle range depended on the flexibility of the D-loop. Additional barbed end bound states were seen when the incoming subunit was in the G-actin form. Consistent with an activation barrier for pointed end polymerization, G-actin did not bind at an F-actin pointed end. In all cases, binding at the barbed end also occurred in a configuration similar to the antiparallel (lower) dimer. Individual monomers bound each other in a short-pitch helix complex in addition to other configurations, with several of them apparently non-productive for polymerization. Simulations with multiple monomers in the F-actin form show assembly into filaments as well as transient aggregates at the barbed end. We discuss the implications of these observations on the kinetic pathway of actin filament nucleation and polymerization and possibilities for future improvements of the coarse-grained model. SIGNIFICANCE Control of actin filament nucleation and elongation has crucial importance to cellular life. We show that coarse-grained molecular dynamics simulations are a powerful tool which can gauge involved mechanisms at reasonable computational cost, while retaining essential features of the fully atomic, yet less computationally tractable, system. Using a knowledge-based potential demonstrates the power of these methods for explaining and reproducing polymerization. Intermediate actin complexes identified in the simulations may play critical roles in the kinetic pathways of actin polymerization which may have been difficult to observe in prior experiments. These methods have been sparsely applied to the actin system, yet have potential to answer many important questions in the field.

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My various thoughts on actin

Cited by 4 publications

References 40 publications

Actin Cytoskeleton and Membrane Interactions: Role in GPCR Function and Organization

Actin Cytoskeleton and Membrane Interactions: Role in GPCR Function and Organization

Computational study of the impact of nucleotide variations on highly conserved proteins: In the case of actin

Insights into Actin Polymerization and Nucleation Using a Coarse-Grained Model

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