Molecule structure offers clue to HIV and cancer treatments

A blood cell infected with the HIV virus The molecule appears to help HIV enter cells

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Scientists have created an image of an important molecule linked to HIV infection and cancer which may help treat the diseases.

Researchers from California used an X-ray technique to find out the structure of the CXCR4 molecule and how it works.

The findings could open up new areas for drug discovery, says the study published in Science.

But experts say we still need to understand more about the activity of CXCR4.

The molecule is part of a large family of proteins called G-protein coupled receptors (GPCRs).

These molecules span the cell's membrane and transmit signals from the external environment to its interior.

They help control practically every bodily process, including cell growth, hormone secretion and light perception.

Start Quote

Unravelling the structure of this molecule is a vital step towards designing new drugs to help treat cancer”

End Quote Josephine Querido Cancer Research UK

Normally CXCR4 helps activate the immune system and stimulate cell movement.

Mixed signals

But when the signals that activate the receptor are not properly regulated, CXCR4 can spur the growth and spread of cancer.

To get a picture of this important molecule, scientists used a method called X-ray crystallography.

But this method proved difficult because membrane proteins are tricky to coax into the crystal form required for the X-ray technique, the study says.

In the end it took three years to produce the right conditions to get a clear picture of the CXCR4 molecule's structure.

Scientists then managed to generate five distinct structures of CXCR4.

The structures showed that CXCR4 molecules form closely linked pairs, confirming data from other experiments.

'Wine glass' structure

Professor Raymond Stevens, lead researcher from Scripps Research Institute in California, said: "The structures open up entire new areas for understanding fundamental principles in chemokine GPCR signalling," he said.

The images also showed that CXCR4 is shaped like two wine glasses touching in a toast.

Researchers said the pictures suggest how to design compounds that regulate CXCR4 activity or block HIV entry into cells.

If developed into drugs, the study says, such compounds could offer new ways to treat HIV infection or cancer.

Keith Alcorn is senior editor at NAM, a charity that supports people living and working with HIV.

"HIV uses a number of receptors to gain entry to cells. Most people with HIV start out with a virus that uses a receptor called CCR5.

"Over time their virus population may switch to using CXCR4, for reasons we still don't fully understand. Several companies have already developed drugs which block the CCR5 receptor.

"A combination of drugs that block both CCR5 and CXCR4 might prove to be a very successful form of HIV treatment, but we need to understand more about the consequences of blocking the activity of CXCR4, because this receptor is also involved in some of the normal immune system functions," he said.

Josephine Querido, senior science information officer at Cancer Research UK, welcomed the research findings.

"This is exciting research as CXCR4 has been linked to the growth and spread of a variety of different cancers. Unravelling the structure of this molecule is a vital step towards designing new drugs to help treat cancer."

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