De novo design of self-assembling helical protein filaments

Shen, Hongfang; Fallas, Jorge A.; Lynch, E.M.; Sheffler, William; Parry, Bradley R.; Jannetty, Nicholas; Decarreau, Justin; Wagenbach, Michael; Vicente, Juan Jesus; Chen, J.; Wang, L.; Dowling, Quinton M.; Oberdorfer, Gustav; Stewart, Lance; Wordeman, Linda; Yoreo, James J. De; Jacobs‐Wagner, Christine; Kollman, Justin M.; Baker, David

doi:10.1126/science.aau3775

Cited by 119 publications

(131 citation statements)

References 38 publications

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“…The design of mesoscale synthetic protein assemblies is becoming increasingly powerful to create new materials [37][38][39] and functions [40][41][42] . Moreover, as we are only beginning to grasp the complexity of proteome self-organization, new approaches are needed for characterizing and understanding mesoscale properties of protein self-assembly in cells [43][44][45][46][47][48] .…”

Section: Discussionmentioning

confidence: 99%

Designer protein assemblies with tunable phase diagrams in living cells

Heidenreich

Georgeson

Locatelli

et al. 2020

Preprint

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The self-organization of proteins into specific assemblies is a hallmark of biological systems. Principles governing protein-protein interactions have long been known. However, principles by which such nanoscale interactions generate diverse phenotypes of mesoscale assemblies, including phase-separated compartments, remains challenging to characterize and understand. To illuminate such principles, we create a system of two proteins designed to interact and form mesh-like assemblies in living cells. We devise a novel strategy to map high-resolution phase diagrams in vivo , which provide mesoscale self-assembly signatures of our system. The structural modularity of the two protein components allows straightforward modification of their molecular properties, enabling us to characterize how point mutations that change their interaction affinity impact the phase diagram and material state of the assemblies in vivo . Both, the phase diagrams and their dependence on interaction affinity were captured by theory and simulations, including out-of-equilibrium effects seen in growing cells. Applying our system to interrogate biological mechanisms of self-assembly, we find that co-translational protein binding suffices to recruit an mRNA to the designed micron-scale structures.

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Section: Discussionmentioning

confidence: 99%

Designer protein assemblies with tunable phase diagrams in living cells

Heidenreich

Georgeson

Locatelli

et al. 2020

Preprint

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“…Furthermore, knowledge of interaction patterns across binding pockets of related targets can be useful in lead optimization for designing compounds with enhanced specificity. In the context of protein design, the knowledge of residue interactions can aid the design of novel proteins (Shen et al 2018) . For example, during the design optimization phase, the interactions that are present in lower energy design candidates can be identified.…”

Section: Discussionmentioning

confidence: 99%

Uncovering patterns of atomic interactions in static and dynamic structures of proteins

Venkatakrishnan

Fonseca

Anthony

et al. 2019

Preprint

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The number of structures and molecular dynamics simulations of proteins is exploding owing to dramatic advances in cryo-electron microscopy, crystallography, and computing. One of the most powerful ways to analyze structural information involves comparisons of interatomic interactions across different structures or simulations of the same protein or related proteins from the same family ( e.g. different GPCRs). Such comparative analyses are of interest to a wide range of researchers but currently prove challenging for all but a few. To facilitate comparative structural analyses, we have developed tools for (i) rapidly computing and comparing interatomic interactions and (ii) interactively visualizing interactions to enable structure-based interpretations. Using these tools, we have developed the Contact Comparison Atlas, a web-based resource for the comparative analysis of interactions in structures and simulations of proteins.

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“…Gonen et al [108] designed protein homo-oligomers that could self-assemble into 2D protein arrays with a maximum thickness of 3 to 8 nm, with a maximum length of 1 μm [108]. Meanwhile, Shen et al designed protein monomers that could self-assemble into filaments that were multiple μm in length [109].…”

Section: Artificial Conductive Matricesmentioning

confidence: 99%

Electrical Energy Storage with Engineered Biological Systems

Salimijazi

Parra²,

Barstow

2019

Preprint

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The availability of renewable energy technologies is increasing dramatically across the globe thanks to their growing maturity. However, large scale electrical energy storage and retrieval will almost certainly be a required in order to raise the penetration of renewable sources into the grid. No present energy storage technology has the perfect combination of high power and energy density, low financial and environmental cost, lack of site restrictions, long cycle and calendar lifespan, easy materials availability, and fast response time. Engineered electroactive microbes could address many of the limitations of current energy storage technologies by enabling rewired carbon fixation, a process that spatially separates reactions that are normally carried out together in a photosynthetic cell and replaces the least efficient with non-biological equivalents. If successful, this could allow storage of renewable electricity through electrochemical or enzymatic fixation of carbon dioxide and subsequent storage as carbon-based energy storage molecules including hydrocarbon and non-volatile polymers at high efficiency. In this article we compile performance data on biological and non-biological component choices for rewired carbon fixation systems and identify pressing research and engineering challenges.

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De novo design of self-assembling helical protein filaments

Cited by 119 publications

References 38 publications

Designer protein assemblies with tunable phase diagrams in living cells

Designer protein assemblies with tunable phase diagrams in living cells

Uncovering patterns of atomic interactions in static and dynamic structures of proteins

Electrical Energy Storage with Engineered Biological Systems

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