Biosynthesis captured in motion

December 23, 2013 by Susan Brown, University of California - San Diego
Biosynthesis captured in motion
Linking carrier proteins (red) to enzymes (blue) that synthesize fatty acids, reveals this snapshot of biosynthesis in action.

( —Chemists have caught molecules in the act of biosynthesis revealing an animated view of how a fundamental piece of cellular machinery operates. The system they observed, a critical metabolic pathway, generates fatty acids, essential components of fats and structures such as cell membranes. Nature published their findings in the early online edition December 22.

Scientists would like to regulate this pathway for diverse purposes: to curb the chaotic growth of cancer cells or harmful bacteria, for example, or to boost the production of oils by algae to be harvested for fuel. But these efforts often fail, for lack of complete information about how molecules involved in the synthesis interact.

"We need to decipher the communication code, to understand how proteins work with each other on a molecular level," said Michael Burkart, a biological chemist at the University of California, San Diego, who led the project in partnership with Shiou-Chuan (Sheryl) Tsai, a biochemist at UC Irvine.

The challenge is that at work are usually in motion. "It's analogous to a huge machine," Tsai said. "We need to know how different parts of the engine fit and work together."

Capturing images of the varying configurations required a team of chemists with complementary areas of expertise. Their joint work has revealed the molecular dance of a carrier protein that protects the growing chain of and ferries it between active sites of the enzymes that assemble it.

Tsai is an expert in x-ray crystallography, a method chemists use to lock proteins in place and generate still images of their structures. The protein this team studied, acyl carrier protein or ACP, proved particularly challenging because it moves so much.

To pin down ACP and other proteins, Burkart's research group has developed a molecular toolkit, a set of small molecules that can lock proteins together in their working configurations.

"Mike pins them, and I take the pictures," said Tsai, who holds appointments in the departments of Molecular Biology and Biochemistry, Chemistry, and Pharmaceutical Sciences at UC Irvine. The strategy resulted in two snapshots, showing two different states of interaction.

Then, working with Stanley Opella, professor of chemistry and biochemistry at UC San Diego, they extended their observation using a different method, , which reveals the motions of the and enzyme in solution. These observations were validated by dynamic modeling of the molecule by a research group led by J. Andrew McCammon, also a professor of chemistry and biochemistry at UC San Diego.

They saw salt bridges form and the enzyme grab helices and pull them apart. The growing chain of fatty acids also loops back into a pocket in the carrier molecule. "We call it the marsupial protein," Burkart says. "It protects its young." That is, until it's time for the product to go.

"We thought this tiny protein was just a transporter," Tsai said. "But when it ejects its cargo, it works like a piston. We see a helical collapse forcing the fatty acid out."

The approach will allow this team to continue to unravel interactions between proteins, a critical step to the successful manipulation of biosynthetic pathways.

Explore further: Reversible method of tagging proteins developed

More information: Trapping the dynamic acyl carrier protein in fatty acid biosynthesis, DOI: 10.1038/nature12810

Related Stories

Reversible method of tagging proteins developed

September 16, 2012

Chemists at UC San Diego have developed a method that for the first time provides scientists the ability to attach chemical probes onto proteins and subsequently remove them in a repeatable cycle.

Fatty acids crucial to embryonic development

December 12, 2013

One classical question in developmental biology is how different tissue types arise in the correct position of the developing embryo. While one signaling pathway that controls this process has been well described, unexpected ...

Researchers make a case for free fatty acids

October 22, 2013

The current global epidemic of obesity-linked diabetes and its associated consequences -cardiovascular, neurological and renal diseases - is a growing public health problem for which therapeutic options are limited.

Researchers find new recipe for novel proteins

December 17, 2013

( —Yale researchers have discovered a targeted way to make proteins not generally found in nature by expanding the information encrypted in the genetic code.

Recommended for you

Bio-renewable process could help 'green' plastic

January 19, 2018

When John Wesley Hyatt patented the first industrial plastic in 1869, his intention was to create an alternative to the elephant tusk ivory used to make piano keys. But this early plastic also sparked a revolution in the ...

Simulations show how atoms behave inside self-healing cement

January 19, 2018

Researchers at Pacific Northwest National Laboratory (PNNL) have developed a self-healing cement that could repair itself in as little as a few hours. Wellbore cement for geothermal applications has a life-span of only 30 ...

Looking to the sun to create hydrogen fuel

January 18, 2018

When Lawrence Livermore scientist Tadashi Ogitsu leased a hydrogen fuel-cell car in 2017, he knew that his daily commute would change forever. There are no greenhouse gases that come out of the tailpipe, just a bit of water ...

A new polymer raises the bar for lithium-sulfur batteries

January 18, 2018

Lithium-sulfur batteries are promising candidates for replacing common lithium-ion batteries in electric vehicles since they are cheaper, weigh less, and can store nearly double the energy for the same mass. However, lithium-sulfur ...


Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.