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Cells Direct Membrane Traffic By Channel Width, Scientists Say

Date:
August 11, 2005
Source:
University of Illinois at Urbana-Champaign
Summary:
For a glycerol molecule, a measly angstrom's difference in diameter is a road-closed sign: You can't squeeze through unless you are a sleek, water-molecule-sized sports car, say scientists at the University of Illinois at Urbana-Champaign. The roadway is in aquaporins, a class of proteins that form trans-membrane channels in cell walls in all forms of life.

Researcher Emad Tajkhorshid stands by a computer-generated simulation of two aquaporins sliced open.
Credit: Photo by Kwame Ross

CHAMPAIGN, Ill. -- For a glycerol molecule, a measly angstrom'sdifference in diameter is a road-closed sign: You can't squeeze throughunless you are a sleek, water-molecule-sized sports car, say scientistsat the University of Illinois at Urbana-Champaign.

The roadway is in aquaporins, a class of proteins that formtrans-membrane channels in cell walls in all forms of life. They allowfor water movement between the cell and its environment. A subfamily ofaquaporins allows slightly larger molecules, such as glycerol, to pass,too. In humans, 11 aquaporins have been identified, mostly in thekidney, brain and lens of the eye. Impaired function has beenimplicated in a variety of diseases.

Aquaporins are a target of scrutiny for the Theoretical andComputational Biophysics Group at the Beckman Institute for AdvancedScience and Technology.

Using steered molecular dynamics, Beckman researchers havesolved a mystery that years of protein crystallography couldn'taccomplish. Reporting in the August issue of Structure, they show thatthe main structural difference that makes an aquaporin a glycerolchannel is a channel that is just a hundred-millionth of a centimeter-- an angstrom -- wider than a normal water channel.

So even if glycerol molecules line up properly, as do watermolecules to pass through a pure water channel (as documented byresearchers in the same lab in 2002), the slightly larger sugarmolecule is out of luck. The point of entry, known as a selectivityfilter, is the most narrow, but there are other tight barriers blockingthe way as well, said Emad Tajkhorshid, assistant director of researchin the Beckman lab.

"Membrane proteins are difficult to crystallize," he said. "Wedon't have the known structure of many of them. There has been a lot ofrecent progress, and for aquaporins we've got four structuresavailable, which is really exceptional for membrane channels."

For the new study, his team focused on two of them. "Both werefrom the same bug, E-coli. One was a pure water channel. The other is aglycerol channel," Tajkhorshid said. "Structurally they are similar.Researchers have tried to convert a water channel to a glycerolchannel, or the other way around, by mutating amino acids that line thepore of the channel, but they have failed."

The E-coli proteins studied were AqpZ, a water channel, andGlpF, a glycerol channel. Side-by-side in computer-generated images thechannels appear virtually identical. The Beckman teamed pushed glycerolthrough the channels, calculated the energetics and looked forbarriers.

"Nature is using a very, very simple idea here," Tajkhorshidsaid. "Just by making a channel narrower, only water is allowed to passthrough the pure water channel; by making it a little bit bigger in theother channel both glycerol, as well as longer, linear sugar molecules,and water can permeate the channel."

While channel sizes had appeared slightly different aftercrystallizing the proteins in the past, researchers believed thechannels could be manipulated by inducing the surrounding amino acidsto create a hydrophobic or semi-hydrophobic lining required forglycerol passage. Success in doing so could have created new targetsfor drug therapies.

However, it turns out, the amino acids are the same around bothchannels, Tajkhorshid said. So his team now is looking beyond the aminoacids directly lining the channel to find what it is that forceschanges in size.

The same principles, he added, likely apply to all selectiveprotein channels. Understanding the principles could provide new,effective pharmaceutical targets to control the channels to help treatdisease.

Study co-authors were group director Klaus Schulten and Yi Wang, a doctoral student in molecular and cell biology.

###

The National Institutes of Health funded the study, which involvedthe use of supercomputers at the Pittsburgh Supercomputer Center andthe National Center for Supercomputing Applications at Illinois.



Story Source:

The above story is based on materials provided by University of Illinois at Urbana-Champaign. Note: Materials may be edited for content and length.


Cite This Page:

University of Illinois at Urbana-Champaign. "Cells Direct Membrane Traffic By Channel Width, Scientists Say." ScienceDaily. ScienceDaily, 11 August 2005. <www.sciencedaily.com/releases/2005/08/050810132837.htm>.
University of Illinois at Urbana-Champaign. (2005, August 11). Cells Direct Membrane Traffic By Channel Width, Scientists Say. ScienceDaily. Retrieved July 24, 2014 from www.sciencedaily.com/releases/2005/08/050810132837.htm
University of Illinois at Urbana-Champaign. "Cells Direct Membrane Traffic By Channel Width, Scientists Say." ScienceDaily. www.sciencedaily.com/releases/2005/08/050810132837.htm (accessed July 24, 2014).

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