Quality-control mechanism found in bacteria

Aug 03, 2012 By Anne Ju

(Phys.org) -- Like quality-control managers in factories, bacteria possess built-in machinery that track the shape and quality of proteins trying to pass through their cytoplasmic membranes, Cornell biomolecular engineers have shown.

This quality-control mechanism is found in the machinery of the twin-arginine translocation (TAT) pathway, which is a export pathway in plants, bacteria and archaea (single-celled microorganisms). The transport of proteins across is a basic life process and understanding how the TAT pathway works could lend insight into, for example, how bacteria become resistant to .

The discovery is a milestone in a 10-plus year study of the TAT pathway led by Matthew DeLisa, associate professor of chemical and biomolecular engineering, and is detailed in , July 30.

"Our first paper on this topic [PNAS, May 13, 2003] suggested that, given the fact that only folded proteins can go through this system, perhaps a quality-control mechanism was embedded in the machinery itself," DeLisa said. "That idea turned out to be controversial, but this most recent paper, we think, reopens that possibility.

"There are no other mechanisms that we're aware of where the transport machinery itself participates directly in the quality control of its . The discovery [of our research] is … paradigm shifting as far as biological transport machinery goes," DeLisa said.

The TAT pathway is remarkable because, unlike other similar processes, the protein cargo passes through the cell membrane in tightly folded shapes, as opposed to long strings. The pathway allows properly folded proteins to pass, while badly folded or damaged ones are not permitted through.

DeLisa and colleagues Mark Rocco, a graduate student, and Dujduan Waraho-Zhmayev, a postdoctoral associate, used an old trick to make this new discovery: They set up a genetic selection experiment that enables researchers to link genetic mutations to the survival of a cell carrying that mutation.

Using a genetic selection for TAT export, they were able to isolate a mutation known as a suppressor in the TAT machinery that allowed the bacteria to survive if they exported misfolded proteins. They concluded that the bacteria's survival was attributed to their ability to export misfolded proteins, which normal in nature wouldn't do. The team's findings provide the first direct evidence for the participation of the TAT machinery in regulating the export of proteins.

The TAT machinery, they speculate, contains a component that senses whether a protein is folded properly and discriminates between folded or unfolded proteins, allowing export of only the well-folded ones.

The new insight into how the TAT pathway regulates the quality of proteins adds to a growing base of science underlying Ithaca biotechnology company Vybion's proprietary antibody development technology called ProCode.

Several years ago, DeLisa's initial research on the TAT pathway formed the basis of several inventions that have been licensed by Vybion, which is using the technology for creating new antibody drugs, particularly for such diseases as Alzheimer's.

"All of these mechanisms, including the quality control feature, together are elements of the ProCode technology and should be useful in the hunt for 'good' antibodies that bind specifically to their target and are very well behaved from a folding standpoint," said DeLisa, who serves on Vybion's advisory board.

The research was supported by National Institutes of Health and the National Science Foundation.

Explore further: Secret life of cells revealed with new technique

Related Stories

Nature's nanomachines harnessed to make drugs

Nov 07, 2006

Many bacteria produce toxins that can threaten human health, however new research into how bacteria secrete these substances is giving clues as to how scientists could harness these processes to produce biopharmaceuticals. ...

Researchers discover new way to form extracellular vesicles

Nov 17, 2011

Researchers at NYU Langone Medical Center have discovered a protein called TAT-5 that affects the production of extracellular vesicles, small sacs of membrane released from the surface of cells, capable of sending signals ...

Selenium may slow march of AIDS

Nov 28, 2008

Increasing the production of naturally occurring proteins that contain selenium in human blood cells slows down multiplication of the AIDS virus, according to biochemists.

Recommended for you

Secret life of cells revealed with new technique

3 minutes ago

(Phys.org) —A new technique that allows researchers to conduct experiments more rapidly and accurately is giving insights into the workings of proteins important in heart and muscle diseases.

In the 'slime jungle' height matters

43 minutes ago

(Phys.org) —In communities of microbes, akin to 'slime jungles', cells evolve not just to grow faster than their rivals but also to push themselves to the surface of colonies where they gain the best access ...

Queuing theory helps physicist understand protein recycling

22 hours ago

We've all waited in line and most of us have gotten stuck in a check-out line longer than we would like. For Will Mather, assistant professor of physics and an instructor with the College of Science's Integrated Science Curriculum, ...

Cow manure harbors diverse new antibiotic resistance genes

Apr 22, 2014

Manure from dairy cows, which is commonly used as a farm soil fertilizer, contains a surprising number of newly identified antibiotic resistance genes from the cows' gut bacteria. The findings, reported in mBio the online ...

User comments : 0

More news stories

In the 'slime jungle' height matters

(Phys.org) —In communities of microbes, akin to 'slime jungles', cells evolve not just to grow faster than their rivals but also to push themselves to the surface of colonies where they gain the best access ...

New alfalfa variety resists ravenous local pest

(Phys.org) —Cornell plant breeders have released a new alfalfa variety with some resistance against the alfalfa snout beetle, which has ravaged alfalfa fields in nine northern New York counties and across ...

Secret life of cells revealed with new technique

(Phys.org) —A new technique that allows researchers to conduct experiments more rapidly and accurately is giving insights into the workings of proteins important in heart and muscle diseases.

Rainbow trout genome sequenced

Using fish bred at Washington State University, an international team of researchers has mapped the genetic profile of the rainbow trout, a versatile salmonid whose relatively recent genetic history opens ...