ABSTRACT
Intercellular epithelial junctions formed by classical cadherins, ß-catenin, and the actin-binding protein α-catenin link the actin cytoskeletons of adjacent cells into a structural continuum. These assemblies transmit forces through the tissue and respond to intracellular and extracellular signals. However, the mechanisms of junctional assembly and regulation are poorly understood. Studies of cadherin-catenin assembly in a number of metazoans have revealed both similarities and unexpected differences in the biochemical properties of the cadherin·catenin complex that likely reflect the developmental and environmental requirements of different tissues and organisms. Here, we report the structural and biochemical characterization of HMP-1, the Caenorhabditis elegans α-catenin homolog, and compare it with mammalian α-catenin. HMP-1 shares overall similarity in structure and actin-binding properties, but displayed differences in conformational flexibility and allosteric regulation from mammalian α-catenin. HMP-1 bound filamentous actin with an affinity in the single micromolar range, even when complexed with the ß-catenin homolog HMP-2 or when present in a complex of HMP-2 and the cadherin homolog HMR-1, indicating that HMP-1 binding to F-actin is not allosterically regulated by the HMP-2·HMR-1 complex. The middle (i.e. M) domain of HMP-1 appeared to be less conformationally flexible than mammalian α-catenin, which may underlie the dampened effect of HMP-2 binding on HMP-1 actin-binding activity compared with that of the mammalian homolog. In conclusion, our data indicate that HMP-1 constitutively binds ß-catenin and F-actin, and although the overall structure and function of HMP-1 and related α-catenins are similar, the vertebrate proteins appear to be under more complex conformational regulation.
Subject(s)
Actins/chemistry , Cadherins/chemistry , Caenorhabditis elegans Proteins/chemistry , Cytoskeletal Proteins/chemistry , alpha Catenin/chemistry , beta Catenin/chemistry , Allosteric Site , Animals , Caenorhabditis elegans , Cell Adhesion , Crystallography, X-Ray , Glutathione Transferase/metabolism , Molecular Dynamics Simulation , Protein Binding , Protein Domains , Rabbits , Structure-Activity Relationship , Vinculin/chemistryABSTRACT
This study examines whether the way that a person makes inferences about unknown events is associated with his or her social relations, more precisely, those characterized by ego network density that reflects the structure of a person's immediate social relation. From the analysis of individual predictions over the Go match between AlphaGo and Sedol Lee in March 2016 in Seoul, Korea, this study shows that the low-density group scored higher than the high-density group in the accuracy of the prediction over a future state of a social event, i.e., the outcome of the first game. We corroborated this finding with three replication tests that asked the participants to predict the following: film awards, President Park's impeachment in Korea, and the counterfactual assessment of the US presidential election. Taken together, this study suggests that network density is negatively associated with vision advantage, i.e., the ability to discover and forecast an unknown aspect of a social event.