Featured Research

from universities, journals, and other organizations

Fast-acting enzymes with two fingers: Switch protein structurally and dynamically explained

Date:
December 19, 2012
Source:
Ruhr-Universitaet-Bochum
Summary:
Researchers have uncovered the mechanism that switches off the cell transport regulating proteins. They were able to resolve in detail how the central switch protein Rab is down-regulated with two "protein fingers" by its interaction partners.

The interaction of Rab (red) and RabGAP (blue) accelerates the cleavage of GTP (multi-coloured). With the FTIR spectroscopy, we receive an accurate picture of the movements in the active centre in the interaction of the proteins (section on the right). The two “fingers” of RabGAP are shown in grey, and part of the Rab protein is shown in yellow. In the top left section, the GTP molecule with its three phosphate groups (orange-red) can be seen.
Credit: Konstantin Gavriljuk

Researchers at the RUB and from the MPI Dortmund have uncovered the mechanism that switches off the cell transport regulating proteins. They were able to resolve in detail how the central switch protein Rab is down-regulated with two "protein fingers" by its interaction partners.

Related Articles


The structural and dynamic data is reported by the researchers led by Prof. Dr. Klaus Gerwert (Chair of Biophysics, RUB) and Prof. Dr. Roger S. Goody (Max Planck Institute for Molecular Physiology, Dortmund, Germany) in the Online Early Edition of the journal PNAS.

"Unlike in the cell growth protein Ras, which is regulated with only one 'finger', we have surprisingly found a two-finger switch-off mechanism in Rab. This throws a completely new light on the functioning of certain enzymes, the small GTPases, to which Rab belongs," Klaus Gerwert explains.

Switch proteins associated with various diseases

Unlike Ras proteins that regulate cell growth, Rab GTPases (also called Rab proteins) control various transport operations between different areas of a cell. If the transport system is disrupted, diseases such as obesity can occur. The Rab proteins work as a switch, just like the Ras proteins. In the "on" state, the high-energy molecule GTP is bound, in the "off" state, the lower-energy GDP. The cleavage of GTP to GDP is catalysed by the so-termed RabGAP proteins. In so doing, GTP is split into GDP and phosphate. The research team observed the underlying reaction in time and space for the first time with the highest possible atomic resolution.

First a snapshot, then a whole film

Using X-ray structure analysis, the researchers first determined the spatial structure of the protein complex. The data showed a finger of the amino acid arginine, and a second finger of glutamine. The arginine finger was already known from Ras. The glutamine finger is new and surprising. RabGAP penetrates into the GTP-binding pocket of Rab with both fingers and accelerates the GTP cleavage over five orders of magnitude. The biophysicists observed this dynamic process in real time using FTIR spectroscopy. "In contrast to X-ray structure analysis, FTIR spectroscopy not only gives us a snapshot of the reaction, but an entire film," says PD Dr. Carsten Kφtting. The result: both catalytic fingers penetrate simultaneously into the GTP-binding pocket and leave it with the phosphate cleaved from the GTP.

Medically interesting mechanism

In their experiment, the researchers examined the protein Rab1b and the RabGAP TBC1D20. Other Rab proteins and RabGAPs are similar to these two representatives. "Thus, we assume that they also interact via a two-finger mechanism," Konstantin Gavriljuk speculates. The ability of the two-finger system to also switch off mutated Rab proteins, i.e. mutated GTPases, could also be medically very interesting. It would be conceivable to develop small molecules that mimic the two-finger mechanism, and thus switch off other mutant GTPases, such as Ras, which emit uncontrolled growth signals and thus are involved in tumour formation.


Story Source:

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


Journal Reference:

  1. K. Gavriljuk, E.-M. Gazdag, A. Itzen, C. Kotting, R. S. Goody, K. Gerwert. Catalytic mechanism of a mammalian Rab{middle dot}RabGAP complex in atomic detail. Proceedings of the National Academy of Sciences, 2012; DOI: 10.1073/pnas.1214431110

Cite This Page:

Ruhr-Universitaet-Bochum. "Fast-acting enzymes with two fingers: Switch protein structurally and dynamically explained." ScienceDaily. ScienceDaily, 19 December 2012. <www.sciencedaily.com/releases/2012/12/121219084056.htm>.
Ruhr-Universitaet-Bochum. (2012, December 19). Fast-acting enzymes with two fingers: Switch protein structurally and dynamically explained. ScienceDaily. Retrieved October 25, 2014 from www.sciencedaily.com/releases/2012/12/121219084056.htm
Ruhr-Universitaet-Bochum. "Fast-acting enzymes with two fingers: Switch protein structurally and dynamically explained." ScienceDaily. www.sciencedaily.com/releases/2012/12/121219084056.htm (accessed October 25, 2014).

Share This



More Plants & Animals News

Saturday, October 25, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

Deep Sea 'mushroom' Could Be Early Branch on Tree of Life

Deep Sea 'mushroom' Could Be Early Branch on Tree of Life

Reuters - Innovations Video Online (Oct. 24, 2014) — Miniature deep sea animals discovered off the Australian coast almost three decades ago are puzzling scientists, who say the organisms have proved impossible to categorise. Academics at the Natural History of Denmark have appealed to the world scientific community for help, saying that further information on Dendrogramma enigmatica and Dendrogramma discoides could answer key evolutionary questions. Jim Drury has more. Video provided by Reuters
Powered by NewsLook.com
Black Bear Cub Goes Sunday Shopping

Black Bear Cub Goes Sunday Shopping

Reuters - Light News Video Online (Oct. 23, 2014) — Price check on honey? Bear cub startles Oregon drugstore shoppers. Rough Cut (no reporter narration). Video provided by Reuters
Powered by NewsLook.com
Dances With Wolves in China's Wild West

Dances With Wolves in China's Wild West

AFP (Oct. 23, 2014) — One man is on a mission to boost the population of wolves in China's violence-wracked far west. The animal - symbol of the Uighur minority there - is under threat with a massive human resettlement program in the region. Duration: 00:41 Video provided by AFP
Powered by NewsLook.com
Breakfast Debate: To Eat Or Not To Eat?

Breakfast Debate: To Eat Or Not To Eat?

Newsy (Oct. 23, 2014) — Conflicting studies published in the same week re-ignited the debate over whether we should be eating breakfast. 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

 

Plants & Animals

Earth & Climate

Fossils & Ruins

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