43 research outputs found
EMatch: an efficient method for aligning atomic resolution subunits into intermediate-resolution cryo-EM maps of large macromolecular assemblies
A method for detecting structural homologs of components in an intermediate resolution cryo-EM map and their spatial configuration is presented
The material properties of a bacterial-derived biomolecular condensate tune biological function in natural and synthetic systems
Intracellular phase separation is emerging as a universal principle for organizing biochemical reactions in time and space. It remains incompletely resolved how biological function is encoded in these assemblies and whether this depends on their material state. The conserved intrinsically disordered protein PopZ forms condensates at the poles of the bacterium Caulobacter crescentus, which in turn orchestrate cell-cycle regulating signaling cascades. Here we show that the material properties of these condensates are determined by a balance between attractive and repulsive forces mediated by a helical oligomerization domain and an expanded disordered region, respectively. A series of PopZ mutants disrupting this balance results in condensates that span the material properties spectrum, from liquid to solid. A narrow range of condensate material properties supports proper cell division, linking emergent properties to organismal fitness. We use these insights to repurpose PopZ as a modular platform for generating tunable synthetic condensates in human cells
Putting the Pieces Together: Integrative Modeling Platform Software for Structure Determination of Macromolecular Assemblies
A set of software tools for building and distributing models of macromolecular assemblies uses an integrative structure modeling approach, which casts the building of models as a computational optimization problem where information is encoded into a scoring function used to evaluate candidate models
The material properties of a bacterial-derived biomolecular condensate tune biological function in natural and synthetic systems.
Using Optically Reversible Spatial Mutations to Dissect the Asymmetric Developmental Program of a Bacterium
Toward an Integrated Structural Model of the 26S Proteasome*
The 26S proteasome is the end point of the ubiquitin-proteasome pathway and degrades ubiquitylated substrates. It is composed of the 20S core particle (CP), where degradation occurs, and the 19S regulatory particle (RP), which ensures substrate specificity of degradation. Whereas the CP is resolved to atomic resolution, the architecture of the RP is largely unknown. We provide a comprehensive analysis of the current structural knowledge on the RP, including structures of the RP subunits, physical protein-protein interactions, and cryoelectron microscopy data. These data allowed us to compute an atomic model for the CP-AAA-ATPase subcomplex. In addition to this atomic model, further subunits can be mapped approximately, which lets us hypothesize on the substrate path during its degradation