Featured Research

from universities, journals, and other organizations

Another Transmembrane Protein Structure Solved By Rockefeller Scientists; Chloride Ion Channel Strikingly Different From Potassium Kin

Date:
January 22, 2002
Source:
Rockefeller University
Summary:
"Why did nature come up with such a structural plan?" ask Rockefeller University professor Roderick MacKinnon and colleagues in their Jan. 17 Nature cover article describing the three-dimensional structure of a type of chloride channel called the ClC.

"Why did nature come up with such a structural plan?" ask Rockefeller University professor Roderick MacKinnon and colleagues in their Jan. 17 Nature cover article describing the three-dimensional structure of a type of chloride channel called the ClC.

Related Articles


The high-resolution crystallographic images published in Nature represent another instance of the Rockefeller scientists’ remarkable knack for visualizing the specialized proteins that provide ports of cellular entry for potassium, sodium, calcium and chloride.

MacKinnon, who is a Howard Hughes Medical Institute investigator, leads a scientific team that is adding unprecedented detail to existing descriptions of the chloride ion channel.

The research findings are seminal for what is bound to be an industry in developing drug targets for ion channel impairments. The ClC chloride channel, which is found in organisms from bacteria to humans, is linked with some heritable diseases of the muscles and kidney. Mutations in another kind of chloride channel, called the CFTR, are responsible for cystic fibrosis, the most common genetic disease in Caucasian populations.

There are many varieties of ion channels. A cousin to the chloride channel, the potassium ion channel, was structurally solved by MacKinnon’s group in 1998. Numerous existing drugs are known to trigger changes to the potassium ion channel, causing a potentially fatal heart disorder called Long QT syndrome. Developing biomedical solutions to the known impairments of ion channels will improve human health considerably.

The channels, also called transmembrane proteins, ingeniously shepherd vital molecules across cellular and intracellular membranes, keeping surrounding structures and biochemistry intact. Each kind of ion channel has selective features that permit only appropriately sized and charged molecules to travel to their destination in the cell or outside of it.

A distinctive hourglass shape, seen for the first time in MacKinnon and colleagues’ research, defines the chloride channel, and provides a striking contrast to the aqueous, pyramid-shaped cavity of the potassium ion channel. The revelation of the hourglass shape brings new insights to the mechanism by which a chloride ion is stabilized inside the channel. MacKinnon and his colleagues' research also greatly clarifies existing biochemical analyses of the chloride channel, begun 20 years ago.

"In a way, the potassium channel is very brash while the chloride channel is more subtle," says MacKinnon. "By working on both channels, we can start to see some themes that nature uses."

The ClC Chloride Channel

Chloride channels sit at the boundary junctures of a cell, allowing negatively charged ions, called anions, to pass through the membrane into the cell cytoplasm or intra-cellular organelles. Once through the channel, the chloride ions carry out important work, such as regulating electrical impulses and stabilizing the resting membrane potential of the cell. The human genome contains at least nine different chloride ion channels.

The chloride channel's hourglass shape helps overcome the energy barrier between the outside of a cell and its internal environment, report MacKinnon and colleagues. "Being charged, ions would rather be in water than in an oily membrane," says MacKinnon. "Nature has to have a mechanism to get the ion across the cell membrane." The chloride ion's negative charge requires different conditions, and a different structural configuration, than the potassium ion's positive charge.

Part of this structural difference lies in the channel's pore composition feature. The two bacterial chloride channels pictured in the Nature paper—from salmonella typhimurium and Escherichia coli—are homodimers, meaning they have two identical subunits composing the overall structure. Each subunit has its own pore for chloride ions to pass through.

The potassium ion channel, by contrast, is a tetramer, meaning its overall structure comprises four identical or similar subunits. These channels have only one pore encircled by the four parts.

"In the potassium channel, we saw that nature used the alpha-helices to accomplish a partial negative charge," says MacKinnon. "In the chloride channel nature flipped the helices around to put the partial positive end of the helix near the chloride ion. It’s very beautiful."

The gating mechanism of the chloride channel also is unique. The crystallographic images from MacKinnon's group reveal a glutamate side chain to the structure that potentially blocks the ion pathway. For the first time, insight to the chloride channel's gating mechanism is revealed.

As with MacKinnon and his colleagues’ work on the potassium ion channels, many refinements to the data presented in Nature will follow. "We will look more closely and try to get pictures of the gating and selectivity features of the ClC chloride channel," says MacKinnon. The team wants to see, atom by atom, what transports the chloride ion so well to its destination.

At The Rockefeller University, postdoctoral fellows Raimund Dutzler and Martine Cadene, Research Scientist Ernest Campbell and Professor Brian Chait as well as MacKinnon conducted this research.

The research was funded by grants from the NIH to Professors Chait and MacKinnon.

John D. Rockefeller founded Rockefeller University in 1901 as The Rockefeller Institute for Medical Research. Rockefeller scientists have made significant achievements, including the discovery that DNA is the carrier of genetic information. The University has ties to 21 Nobel laureates, six of whom are on campus. Rockefeller University scientists have received the award in two consecutive years: neurobiologist Paul Greengard, Ph.D., in 2000 and cell biologist Gόnter Blobel, M.D., Ph.D., in 1999, both in physiology or medicine. At present, 32 faculty are elected members of the U.S. National Academy of Sciences, including the president, Arnold J. Levine, Ph.D. Celebrating its centennial anniversary in 2001, Rockefeller — the nation’s first biomedical research center—continues to lead the field in both scientific inquiry and the development of tomorrow’s scientists.


Story Source:

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


Cite This Page:

Rockefeller University. "Another Transmembrane Protein Structure Solved By Rockefeller Scientists; Chloride Ion Channel Strikingly Different From Potassium Kin." ScienceDaily. ScienceDaily, 22 January 2002. <www.sciencedaily.com/releases/2002/01/020122072415.htm>.
Rockefeller University. (2002, January 22). Another Transmembrane Protein Structure Solved By Rockefeller Scientists; Chloride Ion Channel Strikingly Different From Potassium Kin. ScienceDaily. Retrieved October 25, 2014 from www.sciencedaily.com/releases/2002/01/020122072415.htm
Rockefeller University. "Another Transmembrane Protein Structure Solved By Rockefeller Scientists; Chloride Ion Channel Strikingly Different From Potassium Kin." ScienceDaily. www.sciencedaily.com/releases/2002/01/020122072415.htm (accessed October 25, 2014).

Share This



More Health & Medicine News

Saturday, October 25, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

IKEA Desk Converts From Standing to Sitting With One Button

IKEA Desk Converts From Standing to Sitting With One Button

Buzz60 (Oct. 24, 2014) — IKEA is out with a new convertible desk that can convert from a sitting desk to a standing one with just the push of a button. Jen Markham explains. Video provided by Buzz60
Powered by NewsLook.com
Ebola Protective Suits Being Made in China

Ebola Protective Suits Being Made in China

AFP (Oct. 24, 2014) — A factory in China is busy making Ebola protective suits for healthcare workers and others fighting the spread of the virus. Duration: 00:38 Video provided by AFP
Powered by NewsLook.com
WHO: Millions of Ebola Vaccine Doses by 2015

WHO: Millions of Ebola Vaccine Doses by 2015

AP (Oct. 24, 2014) — The World Health Organization said on Friday that millions of doses of two experimental Ebola vaccines could be ready for use in 2015 and five more experimental vaccines would start being tested in March. (Oct. 24) Video provided by AP
Powered by NewsLook.com
Doctor in NYC Quarantined With Ebola

Doctor in NYC Quarantined With Ebola

AP (Oct. 24, 2014) — An emergency room doctor who recently returned to the city after treating Ebola patients in West Africa has tested positive for the virus. He's quarantined in a hospital. (Oct. 24) Video provided by AP
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