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The discovery of Bombali virus, a new ebolavirus

To date, five species of ebolavirus are known: Zaire virus, Bundibugyo virus, Sudan virus, Tai Forest virus and Reston virus. Four of these species (all but Reston virus) are known to cause severe disease in human.

In this new article we describe the discovery of a new ebolavirus, named Bombali virus (BOMV), found in free-tailed bats in Sierra Leone. Modeling the interaction between the viral GP1 protein and its receptor in humans (NPC1 protein) suggested that this new virus can indeed bind the human protein; thus, mediating viral entry in human cells. Subsequent experimental analysis confirmed this finding. This however, does not imply that BOMV is pathogenic in humans since we still don’t know if the virus is capable of interacting with the human molecular machinery required to fulfill its life cycle.

This research provides strong evidence that bats serve as hosts for ebolaviruses and highlights the importance of wild life surveillance to evaluate the zoonotic risk of emergent viruses.

Most importantly, this study does not intend to create alarm or incite the retaliatory culling of bats.  Bats play an important ecological role as insectivores, pollinators and seed dispersers and killing or disturbing bats does not reduce the risk of transmission. On the contrary, it might enhance the disease transmission by exposing non infected bats.

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A beautiful friendship: Combining X-ray crystallography and cryo-electron microscopy

Trabuco and colleagues introduce a very interesting approach that combines high-resolution data from X-ray crystallography with lower-resolution electron density maps obtained by cryo-electron microscopy (cryo-EM). This method, known as MDFF (molecular dynamics flexible fitting) incorporates two new variables into its MD potential energy function, one that corresponds to a potential derived from the EM data and another variable that aims to preserve the secondary structure of proteins and nucleic acids.

Such combination permits to take the knowledge that you can extract from cryo-EM maps further. It is important to highlight that the EM map represents an ensemble of conformational states even when dealing with a homogeneus dataset. Therefore, it is preferred to show how not just a single fitted structure but a set of differently structures fitted equally well into a single cryo-EM map. Something similar to the ensemble of structures obtained by NMR.

To our knowledge, this is the only method for flexible fitting capable of dealing with nucleic acids and proteins. The authors release newer versions from time to time (they recently incorporated symmetry restraint into the simulation. I would recommend this method to anyone who is planning to apply a flexible fitting method in his/her research.

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Modular evolution and the origins of symmetry

Broom and colleagues study the molecular evolution of protein domains and the origins of the symmetry of a particular protein domain, known as beta-trefoil.A new protein domain is engineered computationally and subsequently characterized structurally.

This paper provides new insights into the evolution of the symmetry of protein domains and into protein engineering. The authors show that the widely adopted domain duplication and divergence model is not the only source for domain evolution. A new evolutionary model is described, according to which a particular subdomain can lead to the assembly of a new symmetry-based protein domain by combining several repeats of the same subdomain. The latter implies that modular evolution is an ongoing process.

The authors computationally designed a new beta-trefoil subdomain and repeated it into a single chain to form a new three-fold globular protein. The model was then expressed, purified, and structurally characterized. The newly designed protein was found to be highly soluble, stable, and functional. Furthermore, while the single subdomain cannot fold by itself, the single chain containing the three copies of the subdomain folds into a single and stable domain. This indicates a significant energy penalty for forming the beta-trefoil fold from separate chains.  The authors also discuss the benefits of internally symmetric structures for protein function.

A new protein domain is engineered computationally and subsequently characterized structurally.  This paper provides new insights into the evolution of the symmetry of protein domains and into protein engineering. The authors show that the widely adopted domain duplication and divergence model is not the only source for domain evolution. A new evolutionary model is described, according to which a particular subdomain can lead to the assembly of a new symmetry-based protein domain by combining several repeats of the same subdomain. The latter implies that modular evolution is an ongoing process.  The authors computationally designed a new beta-trefoil subdomain and repeated it into a single chain to form a new three-fold globular protein. The model was then expressed, purified, and structurally characterized. The newly designed protein was found to be highly soluble, stable, and functional. Furthermore, while the single subdomain cannot fold by itself, the single chain containing the three copies of the subdomain folds into a single and stable domain. This indicates a significant energy penalty for forming the beta-trefoil fold from separate chains.  The authors also discuss the benefits of internally symmetric structures for protein function.