This is the mechanism that helps the virus to block the cell phone defense system

A defense mechanism that holds human cells against viruses such as monovirus, herpes simplex and human papilloma — all viruses with double chain DNA — based on proteins that patrol the cell a modo de sensores del DNA del virus. Es un tipo de defense celular descubierto hace apenas una decada y aún poco estudiado. Cuando las proteins sensor detectan viral DNA se enlazan a él, y salta entonces la alarma: la cella activa sus defensas. But the virus, como en una carrera armamentística, also has proteins capable of blocking this cellular alarm system.

Una de estas proteins que alerta a las cells de la presenza de virus de ADN es el complejo de proteins llamado ku. Científicos del CNIO y de la Universidad de Sussex have now succeeded in characterizing its three-dimensional structure at the atomic level, coupled with viral proteins capable of blocking this complex. The finding, published in the journal Nature Communications, will improve the response to these infections.

The researchers have worked with the Vaccinia virus (utilized in the development of the vaccine against the virus and belonging to the poxvirus family). Two proteins of this virus, called C4 and C16, block their action, thus inactivating the cellular immune response. Conocer la forma de estas proteins, su estructura tridimensional, ayuda a entender cómo lo hacen.

Proteínas como tapones para inactivar el anillo Where

Ku tiene forma de anillo, con un hueco central que utiliza para enhebrase en el ADN. The researchers discovered that the two proteins of the virus came to serve as stoppers that plug this hole, blocking the capacity to recognize the viral DNA (see graphic animation).

The researchers of the CNIO Group of Macromolecular Complexes in Response to DNA Damage, led by Óscar Llorca, have managed to obtain the structure of the C16-Ku complex through electronic cryomicroscopy, a technique that allows visualizing the interactions between the viral protein and human protein.

In this way, the authors of the work have been able to identify which part of the viral protein causes the blockage of Ku. «El heterodímero Ku forma una especie de anillo que es el que se engarza al ADN. The protein of the virus acts as a kind of stopper of this ring, thus blocking the union of the viral DNA, explained Óscar Llorca.

The work was carried out in collaboration with the group of the University of Sussex (United Kingdom) led by the researcher Laurence H. Pearl, who confirmed that the mechanism of action of the C4 protein is very similar to that of C16.

Bloquear Ku para que no ayude a cellu tumorales

The complex that is also present in the nucleus of the cells, but its paper does not alert the presence of the virus unless it repairs our own genetic material when it is damaged.

The group of Llorca studies the role in cancer of protein complexes, which are involved in double chain DNA repair. Cuando estos mecanizas de reparación actuán en célús tumorales están favoriciendo su survivencia, y por tanto el cáncer. Ahora que se sabe, gracias al nuevo trabajo, cómo los viruses bloquean la action de ku, se podría aprender a altera su papel en la repaira de roturas en el ADN and tumor cells.

“The idea of ​​this research came about because if we treat tumor cells before generating DNA damage, we can block the functioning of Ku during the DNA repair process, similar to what viruses do, the treatment will still más eficaz”, indicates Ángel Rivera-Calzada, coauthor principal del trabajo.

De esta forma, uno de los siguientes pasos será evaluar si emular el mechanismo de las proteinas virales para bloquear Ku serviría para desarrollar una estrategia que amplificará el efecto de los tratamientos contra el cáncer.

Imagen - Conocer la forma de estas proteins, su estructura tridimensional, ayuda a entender cómo lo hacen

Conocer la forma de estas proteins, su estructura tridimensional, ayuda a entender cómo lo hacen

“De toda la protina virica, es una porción de unos pocos aminoados la que actua bloqueando la action de Ku”, points out Rivera-Calzada. El primer paso sería confirmar que esos pequeños fragmentos producidos en el laboratorio son capaces de bloquear el recognition del ADN damage Before that, the authors of the work are confident in collaborating with experts from the CNIO in this type of strategies.

Profundizar en su papel contra las infección viricas

In addition, the information obtained could help the development of strategies against the infections caused by this virus. Comparando las sequencias proteicas de los homologós de C4 y C16 en otros viruses de la familia, los researchers han podido observar que las regiones implicadas en la inactivación de Ku están ample conservadas. Entre estos viruses están, por ejemplo, the virus of the smallpox or the virus of the smallpox, que recently ha sido noticia por the appearance of multiple cases in different European countries. Before that, researchers plan future collaborations with groups specializing in virology.

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