Featured Research

from universities, journals, and other organizations

Blocking HIV Multiplication: Structure Elucidation Of 'Kissing Complex'

Date:
August 8, 2008
Source:
CNRS
Summary:
Scientists have used innovative techniques to elucidate the specific recognition mechanisms between AIDS virus RNA and a synthetic RNA. These results should provide a basis for the development of new therapies targeting viral RNA sequences.

Scientists at the Jean-Pierre Ebel(1) Institute of Structural Biology in collaboration with teams at the European Institute of chemistry and biology(2) and Ottawa University have used innovating NMR(3) techniques to elucidate the specific recognition mechanisms between AIDS virus RNA(4) and a synthetic RNA. These results should provide a basis for the development of new therapies targeting viral RNA sequences.

Related Articles


Blocking HIV multiplication in patients is an important field of investigation in the fight against AIDS. One of the main goals of this research is to develop synthetic drugs capable of preventing viral replication after infection. For multiplication, the virus must duplicate its genetic material during a process called replication. During replication, several important cellular factors must bind to a regulatory RNA sequence of the HIV genome called TAR. One of the important AIDS research topics is therefore the development of synthetic RNAs capable of binding with a strong affinity to this regulatory sequence, thereby preventing viral replication.

Scientists at the European Chemistry And Biology Institute first isolated synthetic RNAs capable of specifically binding part of the loop-forming TAR sequence from a bank of more than 100 billion different oligonucleotides(5), (cf. figure: light blue and dark blue). These RNAs, which also form a loop (orange, red and yellow), bind to the TAR sequence by forming a complex structure called a kissing complex due to the pairing(6) of the two RNA loops. Surprisingly, the researchers found that synthetic RNAs which bind with the highest affinity to the TAR sequence all have a pair of GA bases that remain unpaired to those of the TAR part which form a loop.

To understand the role of this base pair and to permit synthesis of RNAs capable of binding more effectively to the viral regulator sequence, it was necessary to precisely elucidate how this binding takes place and define the essential parameters for its stabilization. By developing innovative NMR tools for the structural study of RNAs in solution, IBS and Ottawa University scientists determined with a very high precision the structure of the complex formed by the two RNAs in solution and unraveled the crucial role of the GA base pair. They found that the insertion of a GA pair allows the stabilization of the complex by the pairing of two additional base pairs. They also showed that the GA pair has a determinant role in stabilizing others kissing complexes.

Notes

(1) Institut mixte CEA-CNRS- Joseph Fourier University – Grenoble

(2) CNRS – Inserm unit 869 – Victor Segalen University – Bordeaux

(3) NMR is the phenomenon by which a nucleus of an atom absorbs electromagnetic radiation at a specific frequency in the presence of a high magnetic field. It has applications in physics, chemistry and medical imaging.

(4) RNA carries the genetic blueprint of the virus, like DNA in man

(5) Oligonucleotides are the chemical building blocks of DNA or RNA chains

(6) Pairing : association of RNA bases in pairs


Story Source:

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


Journal Reference:

  1. Van Melckebeke et al. Liquid-crystal NMR structure of HIV TAR RNA bound to its SELEX RNA aptamer reveals the origins of the high stability of the complex. Proceedings of the National Academy of Sciences, 2008; 105 (27): 9210 DOI: 10.1073/pnas.0712121105

Cite This Page:

CNRS. "Blocking HIV Multiplication: Structure Elucidation Of 'Kissing Complex'." ScienceDaily. ScienceDaily, 8 August 2008. <www.sciencedaily.com/releases/2008/08/080807071314.htm>.
CNRS. (2008, August 8). Blocking HIV Multiplication: Structure Elucidation Of 'Kissing Complex'. ScienceDaily. Retrieved March 4, 2015 from www.sciencedaily.com/releases/2008/08/080807071314.htm
CNRS. "Blocking HIV Multiplication: Structure Elucidation Of 'Kissing Complex'." ScienceDaily. www.sciencedaily.com/releases/2008/08/080807071314.htm (accessed March 4, 2015).

Share This


More From ScienceDaily



More Health & Medicine News

Wednesday, March 4, 2015

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

Adults Only Get The Flu Twice A Decade, Researchers Say

Adults Only Get The Flu Twice A Decade, Researchers Say

Newsy (Mar. 4, 2015) Researchers found adults only get the flu about once every five years. Scientists analyzed how a person&apos;s immunity builds up over time as well. Video provided by Newsy
Powered by NewsLook.com
Mount Everest Has a Poop Problem

Mount Everest Has a Poop Problem

Buzz60 (Mar. 4, 2015) With no bathrooms to use, climbers of Mount Everest have been leaving human waste on the mountain for years, and it&apos;s becoming a health issue. Mike Janela (@mikejanela) has more. Video provided by Buzz60
Powered by NewsLook.com
Obamacare's New Supreme Court Battle

Obamacare's New Supreme Court Battle

Washington Post (Mar. 4, 2015) The Affordable Care Act is facing another challenge at the Supreme Court in King v. Burwell, which deals with subsidies for health insurance. The case could cut out a major provision of Obamacare, causing the law to unravel. Here’s what you need to know about the case. Video provided by Washington Post
Powered by NewsLook.com
Investigation Finds Hurt Workers Suffer More In Some States

Investigation Finds Hurt Workers Suffer More In Some States

Newsy (Mar. 4, 2015) ProPublica and NPR&apos;s joint investigation found drastic cuts to workers compensation benefits and employees&apos; access to those benefits. Video provided by Newsy
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