Dataset Information

Dimer asymmetry defines ?-catenin interactions.

ABSTRACT: The F-actin-binding cytoskeletal protein ?-catenin interacts with ?-catenin-cadherin complexes and stabilizes cell-cell junctions. The ?-catenin-?-catenin complex cannot bind F-actin, whereas interactions of ?-catenin with the cytoskeletal protein vinculin appear to be necessary to stabilize adherens junctions. Here we report the crystal structure of nearly full-length human ?-catenin at 3.7-Å resolution. ?-catenin forms an asymmetric dimer where the four-helix bundle domains of each subunit engage in distinct intermolecular interactions. This results in a left handshake-like dimer, wherein the two subunits have remarkably different conformations. The crystal structure explains why dimeric ?-catenin has a higher affinity for F-actin than does monomeric ?-catenin, why the ?-catenin-?-catenin complex does not bind F-actin, how activated vinculin links the cadherin-catenin complex to the cytoskeleton and why ?-catenin but not inactive vinculin can bind F-actin.

SUBMITTER: Rangarajan ES

PROVIDER: S-EPMC3805043 | biostudies-literature | 2013 Feb

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Dimer asymmetry defines α-catenin interactions.

Rangarajan Erumbi S ES Izard Tina T

Nature structural & molecular biology 20130106 2

The F-actin-binding cytoskeletal protein α-catenin interacts with β-catenin-cadherin complexes and stabilizes cell-cell junctions. The β-catenin-α-catenin complex cannot bind F-actin, whereas interactions of α-catenin with the cytoskeletal protein vinculin appear to be necessary to stabilize adherens junctions. Here we report the crystal structure of nearly full-length human α-catenin at 3.7-Å resolution. α-catenin forms an asymmetric dimer where the four-helix bundle domains of each subunit eng ...[more]

PMID: 23292143

Similar Datasets

Project description:The ability to sense and respond to environmental cues is essential for adaptation and survival in living organisms. In bacteria, this process is accomplished by multidomain sensor histidine kinases that undergo autophosphorylation in response to specific stimuli, thereby triggering downstream signaling cascades. However, the molecular mechanism of allosteric activation is not fully understood in these important sensor proteins. Here, we report the full-length crystal structure of a blue light photoreceptor LOV histidine kinase (LOV-HK) involved in light-dependent virulence modulation in the pathogenic bacterium Brucella abortus Joint analyses of dark and light structures determined in different signaling states have shown that LOV-HK transitions from a symmetric dark structure to a highly asymmetric light state. The initial local and subtle structural signal originated in the chromophore-binding LOV domain alters the dimer asymmetry via a coiled-coil rotary switch and helical bending in the helical spine. These amplified structural changes result in enhanced conformational flexibility and large-scale rearrangements that facilitate the phosphoryl transfer reaction in the HK domain.IMPORTANCE Bacteria employ two-component systems (TCSs) to sense and respond to changes in their surroundings. At the core of the TCS signaling pathway is the multidomain sensor histidine kinase, where the enzymatic activity of its output domain is allosterically controlled by the input signal perceived by the sensor domain. Here, we examine the structures and dynamics of a naturally occurring light-sensitive histidine kinase from the pathogen Brucella abortus in both its full-length and its truncated constructs. Direct comparisons between the structures captured in different signaling states have revealed concerted protein motions in an asymmetric dimer framework in response to light. Findings of this work provide mechanistic insights into modular sensory proteins that share a similar modular architecture.

Dataset Information

Dimer asymmetry defines ?-catenin interactions.

Publications

Dimer asymmetry defines α-catenin interactions.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets