Researchers decipher the structure and mechanism of action of a key complex involved in bacteriophage T7 infection

26.08.2019

Scientists from the Institute for Research in Biomedicine (IRB Barcelona), at the Barcelona Science Park, and the Spanish National Research Council (CSIC) have combined cryomicroscopy and crystallography techniques to study the bacteriophage T7. The study, published in Nature Communications, reveals the opening and closing mechanism of the portal protein during the maturation of the viral capsid, the structure that carries the genetic material of the virus. Deciphering how work the Bacteriophages –viruses that infect bacteria– helps us to understand how others pathogenic affect us and, at the same time, they are a new focus of attention for researchers given their potential as an alternative to antibiotics.

 

 

Surface model showing the structure of the tail of the bacteriophage T7 (Image: Ana Cuervo, CNB-CSIC).

A study involving the Spanish National Research Council (CSIC) and the Institute for Research in Biomedicine (IRB Barcelona) has deciphered the structure and mechanism of action of a key complex in infection by the bacteriophage T7 virus. The work is the result of the collaboration of experts in electronic cryomicroscopy of the National Centre for Biotechnology (CSIC) led by José L. Carrascosa and in X-ray crystallography of the Molecular Biology Institute of Barcelona (CSIC) and IRB Barcelona directed by Miquel Coll. By combining the results of the two techniques, the research groups have obtained new data on the mechanism of action of this complex in the process of viral maturation.

“Bacteriophages are viruses that infect bacteria. In addition to their interest as a model, because of their genetic simplicity and high structural complexity, they are now a new focus of attention for researchers because of their potential as an alternative to the use of antibiotics,” explains José L. Carrascosa, a scientist at the National Centre for Biotechnology and co-director of the study.

A viral capsid is formed during the cycle of bacteriophage T7. This structure stores the genetic material of the virus, introducing it through a small entrance channel formed by the portal protein and that is subsequently closed by the virus's tail protein. The mechanism that allowed this “door” to open and close in a controlled manner was unknown until now. 

“These bacterial viruses have a DNA packaging mechanism similar to that of herpes viruses that infect humans. Therefore, deciphering how they work helps us to understand how pathogenic viruses affect us,” says Miquel Coll, a researcher at the Institute of Molecular Biology of Barcelona and IRB Barcelona and co-director of the study. 

First authors of the work, Ana Cuervo, from the National Centre for Biotechnology, and Montserrat Fàbrega-Ferrer, from IRB Barcelona and the Molecular Biology Institute of Barcelona, highlight how “combining electronic cryomicroscopy and synchrotron X-ray crystallography has allowed us not to only to solve the atomic structure of a large complex, which is a technical challenge, but also to define a model of portal opening and closing during the maturation of the viral capsid”. 


Reference article: Ana Cuervo, Montserrat Fàbrega-Ferrer, Cristina Machón, José Javier Conesa, José Javier Fernández, Rosa Pérez-Luque, Mar Pérez-Ruiz, Joan Pous, María Cristina Vega, José L. Carrascosa y Miquel Coll. "Structures of T7 bacteriophage portal and tail suggest a viral DNA retention and ejection mechanism". Nature Communications (2019) DOI: 10.1038/s41467-019-11705-9

► More information: IRB Barcelona website [+]