A virus capsid-like nanocompartment that stores iron and protects bacteria from oxidative stress
TL;DR: Physiological data reveal that few nanocompartments are assembled during vegetative growth, but they increase fivefold upon starvation, protecting cells from oxidative stress through iron sequestration.
Abstract: Living cells compartmentalize materials and enzymatic reactions to increase metabolic efficiency. While eukaryotes use membrane-bound organelles, bacteria and archaea rely primarily on protein-bound nanocompartments. Encapsulins constitute a class of nanocompartments widespread in bacteria and archaea whose functions have hitherto been unclear. Here, we characterize the encapsulin nanocompartment from Myxococcus xanthus, which consists of a shell protein (EncA, 32.5 kDa) and three internal proteins (EncB, 17 kDa; EncC, 13 kDa; EncD, 11 kDa). Using cryo-electron microscopy, we determined that EncA self-assembles into an icosahedral shell 32 nm in diameter (26 nm internal diameter), built from 180 subunits with the fold first observed in bacteriophage HK97 capsid. The internal proteins, of which EncB and EncC have ferritin-like domains, attach to its inner surface. Native nanocompartments have dense iron-rich cores. Functionally, they resemble ferritins, cage-like iron storage proteins, but with a massively greater capacity (~30,000 iron atoms versus ~3,000 in ferritin). Physiological data reveal that few nanocompartments are assembled during vegetative growth, but they increase fivefold upon starvation, protecting cells from oxidative stress through iron sequestration.
Citations
More filters
TL;DR: This review illustrates that a striking structural diversity of protein assemblies is present in nature, and describes structure-function relationship studies for selected classes of protein architectures, and highlights the techniques that enable the characterisation of supramolecular protein structures.
Abstract: Supramolecular protein assemblies are an emerging area within the chemical sciences, which combine the topological structures of the field of supramolecular chemistry and the state-of-the-art chemical biology approaches to unravel the formation and function of protein assemblies. Recent chemical and biological studies on natural multimeric protein structures, including fibers, rings, tubes, catenanes, knots, and cages, have shown that the quaternary structures of proteins are a prerequisite for their highly specific biological functions. In this review, we illustrate that a striking structural diversity of protein assemblies is present in nature. Furthermore, we describe structure–function relationship studies for selected classes of protein architectures, and we highlight the techniques that enable the characterisation of supramolecular protein structures.
252 citations
TL;DR: This review gives some relevant early history of phage lambda, describes recent developments in understanding the molecular biology of lambda's life cycle and describes the molecular nature of lysogeny.
232 citations
Cites background from "A virus capsid-like nanocompartment..."
...…P22, Sf6 and CUS-3 (Lander et al., 2008; Parent et al., 2012a and 2014a; Singh et al., 2013; Rizzo et al., 2014), as well as herpesvirus MCP (Baker et al., 2005), the MCP of an archaea virus with tailed phage morphology (Pietila et al., 2013), and a cellular nanocompartment (McHugh et al., 2014)....
[...]
TL;DR: Findings on the connections between iron storage, cellular iron regulation and ferritin iron recycling that have been explored in unicellular organisms and in animals are discussed.
Abstract: Ferritin is considered the major iron storage protein which maintains a large iron core in its cavity and has ferroxidase activity. There are many types of ferritin particularly in prokaryotes that include the canonical 24-mer FTN molecules, the heme-containing BFR, the smaller 12-mer DPS and the newly recognized EncFtn of encapsulin that forms a very large iron storage compartment. Recent studies show that ferritin function is more dynamic than previous depicted and new mechanisms of ferritin iron recycling are emerging. They participate to the regulation of cellular iron homeostasis as those of ferritin biosynthesis, cooperating also with the iron-dependent mechanism of cellular iron secretion. Some of these basic processes are in common between unicellular and animal cells, and this review aims at discussing the findings on the connections between iron storage, cellular iron regulation and ferritin iron recycling that have been explored in unicellular organisms and in animals. © 2017 IUBMB Life, 69(6):414-422, 2017.
220 citations
Cites background from "A virus capsid-like nanocompartment..."
...The finding that iron is mainly located in the encapsulin compartment suggests that this is a second commitment for the storage of iron and phosphorus and that it is activated under specific conditions, such as starvation during the vegetative state (20)....
[...]
...More recent, it has been suggested that encapsulins may act as the largest iron storage organelles in prokaryotes with a diameter of 24–32 nm and the capacity to accumulate up to 30,000 Fe atoms (20)....
[...]
TL;DR: It is suggested that, although the replication modules of at least some classes of viruses might descend from primordial selfish genetic elements, bona fide viruses evolved on multiple, independent occasions throughout the course of evolution by the recruitment of diverse host proteins that became major virion components.
Abstract: Viruses are the most abundant biological entities on earth and show remarkable diversity of genome sequences, replication and expression strategies, and virion structures. Evolutionary genomics of viruses revealed many unexpected connections but the general scenario(s) for the evolution of the virosphere remains a matter of intense debate among proponents of the cellular regression, escaped genes, and primordial virus world hypotheses. A comprehensive sequence and structure analysis of major virion proteins indicates that they evolved on about 20 independent occasions, and in some of these cases likely ancestors are identifiable among the proteins of cellular organisms. Virus genomes typically consist of distinct structural and replication modules that recombine frequently and can have different evolutionary trajectories. The present analysis suggests that, although the replication modules of at least some classes of viruses might descend from primordial selfish genetic elements, bona fide viruses evolved on multiple, independent occasions throughout the course of evolution by the recruitment of diverse host proteins that became major virion components.
196 citations
TL;DR: Ferritin family proteins are able to mineralise a range of metal ions and can be used in semi-conductor patterning and a commercial application of ferritin as a phosphate removal system for water purification is explored.
155 citations
Cites background from "A virus capsid-like nanocompartment..."
...identified a new class of ferritin-like proteins that are selectively enclosed within the encapsulin shell, which is much larger than the classical ferritin and may present a solution to this contrast problem [63,64]....
[...]
References
More filters
TL;DR: Two unusual extensions are presented: Multiscale, which adds the ability to visualize large‐scale molecular assemblies such as viral coats, and Collaboratory, which allows researchers to share a Chimera session interactively despite being at separate locales.
Abstract: The design, implementation, and capabilities of an extensible visualization system, UCSF Chimera, are discussed. Chimera is segmented into a core that provides basic services and visualization, and extensions that provide most higher level functionality. This architecture ensures that the extension mechanism satisfies the demands of outside developers who wish to incorporate new features. Two unusual extensions are presented: Multiscale, which adds the ability to visualize large-scale molecular assemblies such as viral coats, and Collaboratory, which allows researchers to share a Chimera session interactively despite being at separate locales. Other extensions include Multalign Viewer, for showing multiple sequence alignments and associated structures; ViewDock, for screening docked ligand orientations; Movie, for replaying molecular dynamics trajectories; and Volume Viewer, for display and analysis of volumetric data. A discussion of the usage of Chimera in real-world situations is given, along with anticipated future directions. Chimera includes full user documentation, is free to academic and nonprofit users, and is available for Microsoft Windows, Linux, Apple Mac OS X, SGI IRIX, and HP Tru64 Unix from http://www.cgl.ucsf.edu/chimera/.
35,698 citations
"A virus capsid-like nanocompartment..." refers methods in this paper
...The resulting atomic coordinates were then used to generate the three quasi-equivalent subunits of an asymmetric unit by rigid-body fitting into the corresponding densities and propagated over the icosahedral shell, using Chimera (Pettersen et al, 2004)....
[...]
TL;DR: Coot is a molecular-graphics program designed to assist in the building of protein and other macromolecular models and the current state of development and available features are presented.
Abstract: Coot is a molecular-graphics application for model building and validation of biological macromolecules. The program displays electron-density maps and atomic models and allows model manipulations such as idealization, real-space refinement, manual rotation/translation, rigid-body fitting, ligand search, solvation, mutations, rotamers and Ramachandran idealization. Furthermore, tools are provided for model validation as well as interfaces to external programs for refinement, validation and graphics. The software is designed to be easy to learn for novice users, which is achieved by ensuring that tools for common tasks are `discoverable' through familiar user-interface elements (menus and toolbars) or by intuitive behaviour (mouse controls). Recent developments have focused on providing tools for expert users, with customisable key bindings, extensions and an extensive scripting interface. The software is under rapid development, but has already achieved very widespread use within the crystallographic community. The current state of the software is presented, with a description of the facilities available and of some of the underlying methods employed.
22,053 citations
"A virus capsid-like nanocompartment..." refers methods in this paper
...Manual model building in Coot (Emsley et al, 2010) alternated with automatic refinement....
[...]
TL;DR: The PHENIX software for macromolecular structure determination is described and its uses and benefits are described.
Abstract: Macromolecular X-ray crystallography is routinely applied to understand biological processes at a molecular level. However, significant time and effort are still required to solve and complete many of these structures because of the need for manual interpretation of complex numerical data using many software packages and the repeated use of interactive three-dimensional graphics. PHENIX has been developed to provide a comprehensive system for macromolecular crystallographic structure solution with an emphasis on the automation of all procedures. This has relied on the development of algorithms that minimize or eliminate subjective input, the development of algorithms that automate procedures that are traditionally performed by hand and, finally, the development of a framework that allows a tight integration between the algorithms.
18,531 citations
"A virus capsid-like nanocompartment..." refers methods in this paper
...Finally, the structure was refined using X-ray crystallographic procedures, applying constraints that compensate in part for the limited resolution (Adams et al, 2010)....
[...]
...Structure factors and Hendrickson–Lattman coefficients, describing phases, were calculated using the phenix.map_to_structure_factors program from PHENIX (Adams et al, 2010), and the atomic model was refined with phased maximum-likelihood target as implemented in phenix.refine (Afonine et al, 2005)....
[...]
TL;DR: The CCP4 (Collaborative Computational Project, number 4) program suite is a collection of programs and associated data and subroutine libraries which can be used for macromolecular structure determination by X-ray crystallography.
Abstract: The CCP4 (Collaborative Computational Project, number 4) program suite is a collection of programs and associated data and subroutine libraries which can be used for macromolecular structure determination by X-ray crystallography. The suite is designed to be flexible, allowing users a number of methods of achieving their aims and so there may be more than one program to cover each function. The programs are written mainly in standard Fortran77. They are from a wide variety of sources but are connected by standard data file formats. The package has been ported to all the major platforms under both Unix and VMS. The suite is distributed by anonymous ftp from Daresbury Laboratory and is widely used throughout the world.
17,220 citations
TL;DR: PHENIX has been developed to provide a comprehensive system for macromolecular crystallographic structure solution with an emphasis on the automation of all procedures.
Abstract: Macromolecular X-ray crystallography is routinely applied to understand biological processes at a molecular level. However, significant time and effort are still required to solve and complete many of these structures because of the need for manual interpretation of complex numerical data using many software packages and the repeated use of interactive three-dimensional graphics. PHENIX has been developed to provide a comprehensive system for macromolecular crystallographic structure solution with an emphasis on the automation of all procedures. This has relied on the development of algorithms that minimize or eliminate subjective input, the development of algorithms that automate procedures that are traditionally performed by hand and, finally, the development of a framework that allows a tight integration between the algorithms.
Keywords:
PHENIX;
Python;
algorithms
9,732 citations