Featured Research

from universities, journals, and other organizations

Molecular Espionage Shows A Single HIV Enzyme's Many Tasks

Date:
May 9, 2008
Source:
Harvard University
Summary:
Using ingenious molecular espionage, scientists have found how a single key enzyme, seemingly the Swiss army knife in HIV's toolbox, differentiates and dynamically binds both DNA and RNA as part of the virus' fierce attack on host cells.

Using ingenious molecular espionage, scientists have found how a single key enzyme, seemingly the Swiss army knife in HIV's toolbox, differentiates and dynamically binds both DNA and RNA as part of the virus' fierce attack on host cells. The work is described in the journal Nature.

Related Articles


The enzyme, reverse transcriptase (RT), is already the target of two of the three major classes of existing anti-HIV drugs. The new work, using single-molecule fluorescent imaging to trace RT's activity in real time, not only reveals novel insights into how this critical viral enzyme functions, but also clarifies how some of the anti-HIV pharmaceuticals work.

The research team, at Harvard University and the National Cancer Institute, was led by Xiaowei Zhuang at Harvard and Stuart Le Grice at NCI. Elio A. Abbondanzieri at Harvard and Gregory Bokinsky, formerly at Harvard and now at the Lawrence Berkeley National Laboratory, are lead authors.

"Our experiments allowed us, for the first time, a peek at how individual RT molecules interact with the HIV genome," says Zhuang, professor of chemistry and chemical biology and of physics in Harvard's Faculty of Arts and Sciences, as well as an investigator with the Howard Hughes Medical Institute. "We found that RT binds RNA and DNA primers with opposite orientations and that RT's function is dictated by this binding orientation."

HIV begins its assault by injecting its single-stranded RNA into a host cell. Three subsequent steps are all mediated by RT: The viral RNA is converted into single-stranded DNA, the single-stranded DNA is replicated into double-stranded DNA, and the original viral RNA is degraded. Another enzyme mediates the final step of the genome conversion, where the viral double-stranded DNA is inserted into the host's DNA, allowing it to take advantage of the host's genetic machinery to replicate and propagate itself.

Using their molecular probe to spy on this process, Abbondanzieri and colleagues traced RT's multitasking skill to its dynamic active sites, which allow it to bind and process RNA as well as single- or double-stranded DNA.

"Remarkably, RT can spontaneously flip between these two opposite orientations on DNA and RNA to facilitate two distinct catalytic activities," says Abbondanzieri, a postdoctoral researcher in Harvard's Department of Chemistry and Chemical Biology. "These flipping motions, which have never before been seen in a protein-nucleic acid complex, can be likened to a nanoscale version of a gymnastics routine on a pommel horse."

The 180-degree flipping of RT is regulated by nonnucleoside RT inhibitors (NNRTIs), a major class of anti-HIV drugs. Abbondanzieri and coworkers observed NNRTIs inhibiting HIV activity by accelerating RT's flipping between its two active sites, hindering the enzyme's ability to convert single-stranded DNA to double-stranded DNA.

The other co-authors of the paper are Jennifer X. Zhang at Harvard and Jason W. Rausch at the NCI's HIV Drug Resistance Program. This work was funded by the Howard Hughes Medical Institute, the National Institute of General Medical Sciences, the Packard Foundation, the National Cancer Institute, and the Jane Coffin Childs Memorial Fund.


Story Source:

The above story is based on materials provided by Harvard University. Note: Materials may be edited for content and length.


Cite This Page:

Harvard University. "Molecular Espionage Shows A Single HIV Enzyme's Many Tasks." ScienceDaily. ScienceDaily, 9 May 2008. <www.sciencedaily.com/releases/2008/05/080507133334.htm>.
Harvard University. (2008, May 9). Molecular Espionage Shows A Single HIV Enzyme's Many Tasks. ScienceDaily. Retrieved December 20, 2014 from www.sciencedaily.com/releases/2008/05/080507133334.htm
Harvard University. "Molecular Espionage Shows A Single HIV Enzyme's Many Tasks." ScienceDaily. www.sciencedaily.com/releases/2008/05/080507133334.htm (accessed December 20, 2014).

Share This


More From ScienceDaily



More Health & Medicine News

Saturday, December 20, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

The Best Tips to Curb Holiday Carbs

The Best Tips to Curb Holiday Carbs

Buzz60 (Dec. 19, 2014) It's hard to resist those delicious but fattening carbs we all crave during the winter months, but there are some ways to stay satisfied without consuming the extra calories. Vanessa Freeman (@VanessaFreeTV) has the details. Video provided by Buzz60
Powered by NewsLook.com
Sierra Leone Bikers Spread the Message to Fight Ebola

Sierra Leone Bikers Spread the Message to Fight Ebola

AFP (Dec. 19, 2014) More than 100 motorcyclists hit the road to spread awareness messages about Ebola. Nearly 7,000 people have now died from the virus, almost all of them in west Africa, according to the World Health Organization. Video provided by AFP
Powered by NewsLook.com
Researchers Test Colombian Village With High Alzheimer's Rates

Researchers Test Colombian Village With High Alzheimer's Rates

AFP (Dec. 19, 2014) In Yarumal, a village in N. Colombia, Alzheimer's has ravaged a disproportionately large number of families. A genetic "curse" that may pave the way for research on how to treat the disease that claims a new victim every four seconds. Duration: 02:42 Video provided by AFP
Powered by NewsLook.com
Double-Amputee Becomes First To Move Two Prosthetic Arms With His Mind

Double-Amputee Becomes First To Move Two Prosthetic Arms With His Mind

Buzz60 (Dec. 19, 2014) A double-amputee makes history by becoming the first person to wear and operate two prosthetic arms using only his mind. Jen Markham has the story. Video provided by Buzz60
Powered by NewsLook.com

Search ScienceDaily

Number of stories in archives: 140,361

Find with keyword(s):
Enter a keyword or phrase to search ScienceDaily for related topics and research stories.

Save/Print:
Share:

Breaking News:

Strange & Offbeat Stories


Health & Medicine

Mind & Brain

Living & Well

In Other News

... from NewsDaily.com

Science News

Health News

Environment News

Technology News



Save/Print:
Share:

Free Subscriptions


Get the latest science news with ScienceDaily's free email newsletters, updated daily and weekly. Or view hourly updated newsfeeds in your RSS reader:

Get Social & Mobile


Keep up to date with the latest news from ScienceDaily via social networks and mobile apps:

Have Feedback?


Tell us what you think of ScienceDaily -- we welcome both positive and negative comments. Have any problems using the site? Questions?
Mobile: iPhone Android Web
Follow: Facebook Twitter Google+
Subscribe: RSS Feeds Email Newsletters
Latest Headlines Health & Medicine Mind & Brain Space & Time Matter & Energy Computers & Math Plants & Animals Earth & Climate Fossils & Ruins