Dataset Information

Structural basis of fast- and slow-severing actin-cofilactin boundaries.

ABSTRACT: Members of the ADF/cofilin family of regulatory proteins bind actin filaments cooperatively, locally change actin subunit conformation and orientation, and sever filaments at "boundaries" between bare and cofilin-occupied segments. A cluster of bound cofilin introduces two distinct classes of boundaries due to the intrinsic polarity of actin filaments, one at the "pointed" end side and the other at the "barbed" end-side of the cluster; severing occurs more readily at the pointed end side of the cluster ("fast-severing" boundary) than the barbed end side ("slow-severing" boundary). A recent electron-cryomicroscopy (cryo-EM) model of the slow-severing boundary revealed structural "defects" at the interface that potentially contribute to severing. However, the structure of the fast-severing boundary remains uncertain. Here, we use extensive molecular dynamics simulations to produce atomic resolution models of both severing boundaries. Our equilibrated simulation model of the slow-severing boundary is consistent with the cryo-EM structural model. Simulations indicate that actin subunits at both boundaries adopt structures intermediate between those of bare and cofilin-bound actin subunits. These "intermediate" states have compromised intersubunit contacts, but those at the slow-severing boundary are stabilized by cofilin bridging interactions, accounting for its lower fragmentation probability. Simulations where cofilin proteins are removed from cofilactin filaments favor a mechanism in which a cluster of two contiguously bound cofilins is needed to fully stabilize the cofilactin conformation, promote cooperative binding interactions, and accelerate filament severing. Together, these studies provide a molecular-scale foundation for developing coarse-grained and theoretical descriptions of cofilin-mediated actin filament severing.

SUBMITTER: Hocky GM

PROVIDER: S-EPMC7961102 | biostudies-literature |

REPOSITORIES: biostudies-literature

ACCESS DATA

Similar Datasets

Project description:Endogenously determined inter-individual differences in growth rate of bivalve molluscs have been widely analyzed at different organizational levels. Most studies have focused on the characterization of the physiological differences between fast (F) and slow (S) growing individuals. Although several genes have been described to be up regulated on fast growing individuals, the molecular basis underlying the mechanisms at the origin of growth variation is still poorly understood. In the present study we reared mussel spat of the species Mytilus galloprovincialis under diets below the pseudofaeces threshold (BP) and above the pseudofaeces threshold (AP). After 3 months, F and S mussels on each condition were selected, so that 4 experimental groups were obtained: FBP, SBP, FAP and SAP. We hypothesized that nurturing conditions during their growing period would modify the molecular basis of growth rate differences. However, results of feeding experiments showed that F mussels displayed higher clearance and ingestion rates and higher efficiencies of food selection prior to ingestion, as well as higher gill surface areas, irrespective of the rearing nutritional environment. To decipher molecular mechanism at the origin of growth variation, gills of the 4 mussel groups were dissected, and used for transcriptome analysis with a custom Agilent single channel microarray. Gene expression analysis revealed i) a low number (12) of genes differentially expressed associated to maintenance condition differences and ii) 117 genes differentially expressed when comparing fast and slow growing mussels (FBP + FAP vs. SBP + SAP). We further investigated this comparison: GO terms and KEGG pathway association of the differentially expressed genes allowed us to analyze the functions involved on the differentially expressed encoding. Transcriptomic differences between F and S mussels were mainly based on the up-regulation of response to stimulus, growth and cell activity Biological Process GO terms. Regarding the KEGG terms, carbohydrate metabolism and Krebs cycle were found to be up-regulated in F mussels whereas biosynthetic processes were up-regulated in S mussels. Among the differentially expressed genes that are annotated, the following ones were found to be up regulated in F mussels: i) Mucin, related to mucus secretion, known to be crucial in food acquisition and pre-ingestive selection processes in bivalves, ii) genes related to growth such as Myostatin or Insulin-like growth factor, iii) genes involved in feeding activity, such as Fibrocystin or Dynein and iv) genes involved in the energetic metabolism; Citrate synthase. S mussels mainly over-expressed genes related to immune system and defence (Leucine-rich repeat-containing protein, Metalloendopeptidase, Small heat shock protein 24, Multidrug resistance,…).The present results suggest that differences in feeding activity and in the allocation of metabolic energy between growth groups could account for the differences in growth rate in spat of Mytilus galloprovincialis. In accordance with their higher feeding rates and growth, fast growing mussels were found to mainly over-express genes involved in the development and maintenance of such activities, however, slow growing mussels needed to expend energy in immune and defence processes to ensure survival at the expense of growth rate.

Dataset Information

Structural basis of fast- and slow-severing actin-cofilactin boundaries.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets