Matrix protein key to fighting viruses

Apr 29, 2009
Detailed surface features of the matrix protein

Researchers from Durham University's Centre for Bioactive Chemistry are developing methods that show how proteins interact with cell membranes when a virus strikes. Using their approach, the team hopes to find new ways to disrupt and disarm 'enveloped viruses' before they spread in our bodies.

Team members, Dr John Sanderson and Dr Paul Yeo from Durham University have helped produce the first ever, high-resolution, full-length structure of a protein from an enveloped virus called the 'matrix protein'.

Viruses work in many different ways but in this case, respiratory syncytial virus (RSV) virions form by a 'budding' process at the of a cell. The matrix protein appears to drive the final assembly process and the formation of viral filaments. It is also clear that the matrix protein is an important determinant of where the virus buds.

Using x-ray crystallography, the team's been able to see the intimate details of the matrix protein that controls how the RSV virus assembles inside a cell. The technique allows them to see how the virus protein functions and this could help the team to develop biochemical tools to treat respiratory ailments and the common cold.

Dr Yeo said: "We can now see what the protein virus structure looks like and we plan to pull the protein apart to see how and where it might be intercepted. These images provide amazing insights into the micro-chemical world of our cells. We have an opportunity to use bioactive chemistry to develop the medical tools of the future."

The team, funded by Durham University, the Wolfson Institute and One North East, looked at the matrix protein of (RSV), a virus which is the most dangerous respiratory virus affecting infants and for which there is no vaccine. About one in three people suffering a cold are affected by this particular enveloped virus. They are looking at the way in which the matrix protein pulls the virus together and assembles at the membrane of a cell. This interaction is crucial to the development of cellular disease.

Dr John Sanderson said; "Enveloped viruses can be extremely dangerous. They enter the cell and hijack its machinery. They assemble their own cell parts of proteins and nucleic acids, before pinching off a bit of the membrane lining of a cell, in this case the lung, and going on to infect new cells. Our new hi-resolution structure can help us to see how to disrupt that process."

Durham's researchers have looked closely at the different stages of virus assembly and replication and they are particularly interested at the stage where the virus assembles. It's at this stage that they intend to disrupt the protein.

Dr Paul Yeo said: "If you can intercept the virus at the right time, just before it exits the cell, then your immune system can deal with it. Almost all envelope viruses have to assemble and we want to see how the mechanism works, how the virus latches on to and how it buds inside them."

The researchers grew crystals of the protein, crystallised them, and then used x-ray diffraction to determine the position in space of every atom of the protein. The information was then used to create images of the protein's structure. These images enable the team see what different parts of the matrix protein do.

If scientists can understand how the protein binds to cell membranes, then chemists and biological scientists may be able to develop tools to stop the protein mechanism working; this could be a stepping stone to the development of drugs to fight viruses like RSV. The Durham team also hope to work on other viruses such as Hepatitis C and measles.

Dr Sanderson said: "The high-resolution and degree of crystallographic order that we've observed in the structure allows us to throw light on the way in which the membrane binds, and on the mechanism by which this protein performs its varied and critical roles. It's an exciting development that could help in the quest for the biochemical tools of the future."

The 5 stages of virus assembly and replication:

  1. Entry into the cell
  2. Replication of genome
  3. Production of the components of the
  4. Coordinated assembly
  5. Exit from the cell and release (and multiplication)

Source: Durham University (news : web)

Explore further: Abnormal properties of cancer protein revealed in fly eyes

add to favorites email to friend print save as pdf

Related Stories

Structure of salt lake archaeal virus solved in Finland

May 27, 2008

Researchers at the Finnish Centre of Excellence in Virus Research at University of Helsinki’s Institute of Biotechnology have solved the structure of archaeal virus SH1 to the resolution of one nanometer. The results that ...

Penn researchers discover new mechanism for viral replication

Aug 16, 2007

Researchers at the University of Pennsylvania School of Medicine have identified a new strategy that Kaposi’s Sarcoma Associated Herpesvirus (KSHV) uses to dupe infected cells into replicating its viral genome. This allows ...

A tricky tumor virus

Jan 17, 2008

Epstein-Barr virus (EBV) is a human-pathogenic virus which belongs to the herpes virus family. Almost every adult carries EBV inside. With an infestation rate of more than 90 %, EBV is one of the most successful human viruses. ...

Recommended for you

Chemical biologists find new halogenation enzyme

Sep 15, 2014

Molecules containing carbon-halogen bonds are produced naturally across all kingdoms of life and constitute a large family of natural products with a broad range of biological activities. The presence of halogen substituents ...

Protein secrets of Ebola virus

Sep 15, 2014

The current Ebola virus outbreak in West Africa, which has claimed more than 2000 lives, has highlighted the need for a deeper understanding of the molecular biology of the virus that could be critical in ...

Protein courtship revealed through chemist's lens

Sep 15, 2014

Staying clear of diseases requires that the proteins in our cells cooperate with one another. But, it has been a well-guarded secret how tens of thousands of different proteins find the correct dancing partners ...

User comments : 0