Cornell researchers reveal structure of key protein

Apr 21, 2010
Crystal structure of the yeast Sac1 protein, left, and rotated 90 degrees, right.

(PhysOrg.com) -- For the first time, researchers -- all Cornell scientists -- have characterized the structure of a protein that belongs to certain enzymes that are essential for proper functioning in all life forms, from yeast to humans.

The enzymes, belonging to the so-called Sac family, are involved in cellular signaling and membrane trafficking. Scientists have found that when the gene that expresses Sac enzymes is deleted in animals, the animals die, and mutations of related genes in humans lead to cancers and such neurodegenerative hereditary diseases as Charcot-Marie-Tooth Type 4J (CMT4J) and Lou Gehrig's disease.

Researchers from Cornell's Weill Institute of Cell and Molecular Biology, reporting online in the Journal of the European Molecular Biology Organization, have characterized for the first time the of the Sac1 protein in yeast. Yeast serves as a for all cells; most of the 6,000 genes in yeast are also found in humans. The Sac1 protein in yeast is a progenitor for related Sac proteins also found in plants and animals.

Understanding the Sac1 protein's structure opens the way for experiments that may reveal how these fundamental enzymes interact with cell membranes to enable essential cellular processes, which could also lead to drugs that target related diseases.

"This was first discovered in 1989, but no one had seen the atomic structure of this protein," said Yuxin Mao, an assistant professor of molecular biology and genetics and the paper's senior author. Andrew Manford, a graduate student in the lab of Scott Emr, director of the Weill Institute, is the paper's lead author. "Others have tried, but this is the first time" the protein's structure has been revealed, said Mao.

Much like an on and off switch, pathways that signal cells to divide, migrate or transport materials in and out of the cell are often activated by attaching a phosphate group to proteins or lipids (a process called phosphorylation) and similarly deactivated by the removal of the phosphate group. A class of enzymes called phosphatases mediates the removal of phosphates, and the Sac family of enzymes the Cornell researchers studied are lipid phosphatases. Such diseases as CMT4J and Lou Gehrig's disease occur when Sac family phosphatases fail to function properly, leading to a buildup of a group of phosphorylated lipids.

Mao and colleagues determined the structure by growing Sac protein crystals, which allowed researchers to view a protein's atomic structure through X-ray diffraction. Mao's lab used Cornell's synchrotron to solve the crystal structure of the Sac1 protein at an atomic resolution of less than 2 angstroms (two ten-millionths of a millimeter).

"This opens up biochemical studies of how these enzymes function -- it's a breakthrough in this direction of study," said Mao. "And it helps our studies of other members of the Sac family."

Explore further: Top Japan lab dismisses ground-breaking stem cell study

Related Stories

Study reveals the regulatory mechanism of key enzyme

Sep 20, 2007

Research conducted at the University of California, San Diego (UCSD) School of Medicine has shed new light on the structure and function of one of the key proteins in all mammalian cells, protein kinase A ...

How protein receptors on cells switch on and off

Jan 16, 2009

Cornell researchers have provided new insight into the molecular mechanism underlying an essential cellular system. They have discovered how receptors on cell surfaces turn off signals from the cell's environment, ...

Recommended for you

Top Japan lab dismisses ground-breaking stem cell study

Dec 26, 2014

Japan's top research institute on Friday hammered the final nail in the coffin of what was once billed as a ground-breaking stem cell study, dismissing it as flawed and saying the work could have been fabricated.

Research sheds light on what causes cells to divide

Dec 24, 2014

When a rapidly-growing cell divides into two smaller cells, what triggers the split? Is it the size the growing cell eventually reaches? Or is the real trigger the time period over which the cell keeps growing ...

Locking mechanism found for 'scissors' that cut DNA

Dec 24, 2014

Researchers at Johns Hopkins have discovered what keeps an enzyme from becoming overzealous in its clipping of DNA. Since controlled clipping is required for the production of specialized immune system proteins, ...

Scrapie could breach the species barrier

Dec 24, 2014

INRA scientists have shown for the first time that the pathogens responsible for scrapie in small ruminants (prions) have the potential to convert the human prion protein from a healthy state to a pathological ...

Extracting bioactive compounds from marine microalgae

Dec 24, 2014

Microalgae can produce high value health compounds like omega-3s , traditionally sourced from fish. With declining fish stocks, an alternative source is imperative. Published in the Pertanika Journal of Tr ...

User comments : 0

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.