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Communications Biology Sep 2023Actin, an important component of eukaryotic cell cytoskeleton, regulates cell shape and transport. The morphology and biochemical properties of actin filaments are...
Actin, an important component of eukaryotic cell cytoskeleton, regulates cell shape and transport. The morphology and biochemical properties of actin filaments are determined by their structure and protein-protein contacts. Crowded environments can organize filaments into bundles, but less is known about how they affect F-actin structure. This study used 2D IR spectroscopy and spectral calculations to examine how crowding and bundling impact the secondary structure and local environments in filaments and weakly or strongly bundled networks. The results reveal that bundling induces changes in actin's secondary structure, leading to a decrease in β-sheet and an increase in loop conformations. Strongly bundled networks exhibit a decrease in backbone solvent exposure, with less perturbed α-helices and nearly "locked" β-sheets. Similarly, the loops become less hydrated but maintain a dynamic environment. These findings highlight the role of loop structure in actin network morphology and stability under morphology control by PEG.
Topics: Actins; Actin Cytoskeleton; Protein Structure, Secondary; Cytoskeleton; Cell Shape
PubMed: 37660224
DOI: 10.1038/s42003-023-05274-3 -
Anatomical Record (Hoboken, N.J. : 2007) Dec 2018
Topics: Actins; Animals; Cell Membrane; Humans; Intracellular Membranes; Protein Structural Elements
PubMed: 30418687
DOI: 10.1002/ar.24023 -
Journal of Muscle Research and Cell... Dec 2012The thin filaments of differentiated smooth muscle cells are composed of actin and tropomyosin isoforms and numerous ancillary actin-binding proteins that assemble... (Review)
Review
The thin filaments of differentiated smooth muscle cells are composed of actin and tropomyosin isoforms and numerous ancillary actin-binding proteins that assemble together into distinct thin filament classes. These different filament classes are segregated in smooth muscle cells into structurally and functionally separated contractile and cytoskeletal cellular domains. Typically, thin filaments in smooth muscle cells have been considered to be relatively stable structures like those in striated cells. However, recent efforts have shown that smooth muscle thin filaments indeed are dynamic and that remodeling of the actin cytoskeleton, in particular, regulates smooth muscle function. Thus, the cytoskeleton of differentiated smooth muscle cells appears to function midway between that of less dynamic striated muscle cells and that of very plastic proliferative cells such as fibroblasts. Michael and Kate Bárány keenly followed and participated in some of these studies, consistent with their broad interest in actin function and smooth muscle mechanisms. As a way of honoring the memory of these two pioneer members of the muscle research community, we review data on distribution and remodeling of thin filaments in smooth muscle cells, one of the many research topics that intrigued them.
Topics: Actins; Animals; Cytoskeleton; Humans; Models, Molecular; Molecular Structure; Muscle Contraction; Muscle, Smooth
PubMed: 22311558
DOI: 10.1007/s10974-012-9283-z -
PloS One 2017Histones are small polycationic proteins complexed with DNA located in the cell nucleus. Upon apoptosis they are secreted from the cells and react with extracellular...
Histones are small polycationic proteins complexed with DNA located in the cell nucleus. Upon apoptosis they are secreted from the cells and react with extracellular polyanionic compounds. Actin which is a polyanionic protein, is also secreted from necrotic cells and interacts with histones. We showed that both histone mixture (histone type III) and the recombinant H2A histone bundles F-actin, increases the viscosity of the F-actin containing solution and polymerizes G-actin. The histone-actin bundles are relatively insensitive to increase of ionic strength, unlike other polycation, histatin, lysozyme, spermine and LL-37 induced F-actin bundles. The histone-actin bundles dissociate completely only in the presence of 300-400 mM NaCl. DNA, which competes with F-actin for histones, disassembles histone induced actin bundles. DNase1, which depolymerizes F- to G-actin, actively unbundles the H2A histone induced but slightly affects the histone mixture induced actin bundles. Cofilin decreases the amount of F-actin sedimented by low speed centrifugation, increases light scattering and viscosity of F-actin-histone mixture containing solutions and forms star like superstructures by copolymerizing G-actin with H2A histone. The results indicate that histones are tightly attached to F-actin by strong electrostatic and hydrophobic forces. Since both histones and F-actin are present in the sputum of patients with cystic fibrosis, therefore, the formation of the stable histone-actin bundles can contribute to the pathology of this disease by increasing the viscosity of the sputum. The actin-histone interaction in the nucleus might affect gene expression.
Topics: Actins; Fluorescence; Histones; Hydrophobic and Hydrophilic Interactions; Polymerization; Protein Conformation; Static Electricity
PubMed: 28846729
DOI: 10.1371/journal.pone.0183760 -
Biophysical Journal Dec 2013Actin assembly, filament mechanical properties, and interactions with regulatory proteins depend on the types and concentrations of salts in solution. Salts modulate... (Review)
Review
Actin assembly, filament mechanical properties, and interactions with regulatory proteins depend on the types and concentrations of salts in solution. Salts modulate actin through both nonspecific electrostatic effects and specific binding to discrete sites. Multiple cation-binding site classes spanning a broad range of affinities (nanomolar to millimolar) have been identified on actin monomers and filaments. This review focuses on discrete, low-affinity cation-binding interactions that drive polymerization, regulate filament-bending mechanics, and modulate interactions with regulatory proteins. Cation binding may be perturbed by actin post-translational modifications and linked equilibria. Partial cation occupancy under physiological and commonly used in vitro solution conditions likely contribute to filament mechanical heterogeneity and structural polymorphism. Site-specific cation-binding residues are conserved in Arp2 and Arp3, and may play a role in Arp2/3 complex activation and actin-filament branching activity. Actin-salt interactions demonstrate the relevance of ion-linked equilibria in the operation and regulation of complex biological systems.
Topics: Actin-Related Protein 2-3 Complex; Actins; Amino Acid Sequence; Animals; Cations, Divalent; Humans; Molecular Sequence Data; Protein Binding; Protein Multimerization
PubMed: 24359734
DOI: 10.1016/j.bpj.2013.10.032 -
Microbiology and Molecular Biology... Dec 2006Recent advances have shown conclusively that bacterial cells possess distant but true homologues of actin (MreB, ParM, and the recently uncovered MamK protein). Despite... (Review)
Review
Recent advances have shown conclusively that bacterial cells possess distant but true homologues of actin (MreB, ParM, and the recently uncovered MamK protein). Despite weak amino acid sequence similarity, MreB and ParM exhibit high structural homology to actin. Just like F-actin in eukaryotes, MreB and ParM assemble into highly dynamic filamentous structures in vivo and in vitro. MreB-like proteins are essential for cell viability and have been implicated in major cellular processes, including cell morphogenesis, chromosome segregation, and cell polarity. ParM (a plasmid-encoded actin homologue) is responsible for driving plasmid-DNA partitioning. The dynamic prokaryotic actin-like cytoskeleton is thought to serve as a central organizer for the targeting and accurate positioning of proteins and nucleoprotein complexes, thereby (and by analogy to the eukaryotic cytoskeleton) spatially and temporally controlling macromolecular trafficking in bacterial cells. In this paper, the general properties and known functions of the actin orthologues in bacteria are reviewed.
Topics: Actins; Bacteria; Bacterial Proteins; Cytoskeleton; Escherichia coli Proteins
PubMed: 17158703
DOI: 10.1128/MMBR.00014-06 -
JCI Insight Aug 2020Actin γ 2, smooth muscle (ACTG2) R257C mutation is the most common genetic cause of visceral myopathy. Individuals with ACTG2 mutations endure prolonged...
Actin γ 2, smooth muscle (ACTG2) R257C mutation is the most common genetic cause of visceral myopathy. Individuals with ACTG2 mutations endure prolonged hospitalizations and surgical interventions, become dependent on intravenous nutrition and bladder catheterization, and often die in childhood. Currently, we understand little about how ACTG2 mutations cause disease, and there are no mechanism-based treatments. Our goal was to characterize the effects of ACTG2R257C on actin organization and function in visceral smooth muscle cells. We overexpressed ACTG2WT or ACTG2R257C in primary human intestinal smooth muscle cells (HISMCs) and performed detailed quantitative analyses to examine effects of ACTG2R257C on (a) actin filament formation and subcellular localization, (b) actin-dependent HISMC functions, and (c) smooth muscle contractile gene expression. ACTG2R257C resulted in 41% fewer, 13% thinner, 33% shorter, and 40% less branched ACTG2 filament bundles compared with ACTG2WT. Curiously, total F-actin probed by phalloidin and a pan-actin antibody was unchanged between ACTG2WT- and ACTG2R257C-expressing HISMCs, as was ultrastructural F-actin organization. ACTG2R257C-expressing HISMCs contracted collagen gels similar to ACTG2WT-expressing HISMCs but spread 21% more and were 11% more migratory. In conclusion, ACTG2R257C profoundly affects ACTG2 filament bundle structure, without altering global actin cytoskeleton in HISMCs.
Topics: Actin Cytoskeleton; Actins; Cell Movement; Cells, Cultured; Collagen; Gene Expression Regulation; Humans; Intestinal Pseudo-Obstruction; Muscle Contraction; Muscle, Smooth; Mutation
PubMed: 32814715
DOI: 10.1172/jci.insight.140604 -
Current Biology : CB Feb 2012The field of mechanobiology has witnessed an explosive growth over the past several years as interest has greatly increased in understanding how mechanical forces are... (Review)
Review
The field of mechanobiology has witnessed an explosive growth over the past several years as interest has greatly increased in understanding how mechanical forces are transduced by cells and how cells migrate, adhere and generate traction. Actin, a highly abundant and anomalously conserved protein, plays a large role in forming the dynamic cytoskeleton that is so essential for cell form, motility and mechanosensitivity. While the actin filament (F-actin) has been viewed as dynamic in terms of polymerization and depolymerization, new results suggest that F-actin itself may function as a highly dynamic tension sensor. This property may help explain the unusual conservation of actin's sequence, as well as shed further light on actin's essential role in structures from sarcomeres to stress fibers.
Topics: Actin Cytoskeleton; Actins; Mechanotransduction, Cellular; Models, Molecular; Protein Structure, Tertiary
PubMed: 22321312
DOI: 10.1016/j.cub.2011.12.010 -
Current Opinion in Cell Biology Feb 1996A family of proteins has been discovered over the past three years whose members have clear sequence homology to actin but are distinguished from actin by their... (Review)
Review
A family of proteins has been discovered over the past three years whose members have clear sequence homology to actin but are distinguished from actin by their structural and functional diversity. The ranks of this family, whose members are known as the actin-related proteins (arps), are expanding rapidly. Arps are but one branch of a larger superfamily which includes the actins, hsp/hsc70s, sugar kinases and several cell cycle proteins from bacteria. The existence of the superfamily has been inferred from tertiary structural data. In the case of the arps, their identification and classification has been based upon primary structural data. Placing the arps in a functional context is proving a slower process, although genetic and biochemical analyses are converging in several cases. In the past year, different arps have been linked to functions mediated by actin filaments (arp2 and arp3), microtubules (arp1) and the structural elements of chromatin (arp4 and arp6).
Topics: Actins; Animals; Humans
PubMed: 8791406
DOI: 10.1016/s0955-0674(96)80045-7 -
Current Opinion in Cell Biology Feb 2011In cells the de novo nucleation of actin filaments from monomers requires actin-nucleating proteins. These fall into three main families--the Arp2/3 complex and its... (Review)
Review
In cells the de novo nucleation of actin filaments from monomers requires actin-nucleating proteins. These fall into three main families--the Arp2/3 complex and its nucleation promoting factors (NPFs), formins, and tandem-monomer-binding nucleators. In this review, we highlight recent advances in understanding the molecular mechanism of actin nucleation by both well-characterized and newly identified nucleators, and explore current insights into their cellular functions in membrane trafficking, cell migration and division. The mechanisms and functions of actin nucleators are proving to be more complex than previously considered, with extensive cooperation and overlap in their cellular roles.
Topics: Actin Cytoskeleton; Actins; Animals; Cell Division; Cell Movement; Cells; Humans; Models, Biological
PubMed: 21093244
DOI: 10.1016/j.ceb.2010.10.007