Nanotechnology Now

Our NanoNews Digest Sponsors


Heifer International

Wikipedia Affiliate Button


DHgate

Home > Press > A cellular housekeeper, and potential target of obesity drugs, caught in action

New clues emerge about how a molecular machine breaks down unwanted proteins in cells thanks to work conducted at Berkeley Lab's Advanced Light Source. In this atomic-scale model of the molecular machine, tripeptidyl peptidase II, the cyan ribbon depicts the skeleton of the giant molecule. The grey enclosure represents the lower resolution surface and is included to aid visualization.
New clues emerge about how a molecular machine breaks down unwanted proteins in cells thanks to work conducted at Berkeley Lab's Advanced Light Source. In this atomic-scale model of the molecular machine, tripeptidyl peptidase II, the cyan ribbon depicts the skeleton of the giant molecule. The grey enclosure represents the lower resolution surface and is included to aid visualization.

Abstract:
Scientists from the U.S. Department of Energy's Lawrence Berkeley National Laboratory have obtained the closest look yet of how a gargantuan molecular machine breaks down unwanted proteins in cells, a critical housekeeping chore that helps prevent diseases such as cancer.

A cellular housekeeper, and potential target of obesity drugs, caught in action

Berkeley, CA | Posted on August 2nd, 2010

They pieced together the molecular-scale changes the machine undergoes as it springs into action, ready to snip apart a protein.

Their work provides valuable clues as to how the molecular machine, a giant enzyme called tripeptidyl peptidase II, keeps cells tidy and disease free. It could also inform the development of obesity-fighting drugs. A closely related enzyme in the brain can cause people to feel hungry even after they eat a hearty meal.

"We can now better understand how this very important enzyme carries out its work, which has not been described at a molecular scale until now," says Bing Jap, a biophysicist in Berkeley Lab's Life Sciences Division. He led the research with scientists from the University of California at Berkeley and Germany's Max Planck Institute of Biochemistry.

The scientists report their research August 1 in an advance online publication of the journal Nature Structural & Molecular Biology.

Tripeptidyl peptidase II is found in all eukaryotic cells, which are cells that a have membrane-bound nucleus. Eukaryotic cells make up plants and animals. The enzyme's chief duty is to support the pathway that ensures that cells remain healthy and clutter free by breaking down proteins that are misfolded or have outlived their usefulness.

It's not always so helpful, however. A variation of the enzyme in the brain degrades a hormone that makes people feel satiated after a meal. When this hormone becomes unavailable, a person can eat and eat without feeling full, which can lead to obesity.

Tripeptidyl peptidase II is also the largest protein-degrading enzyme, or protease, in eukaryotic cells. It's more than 100 times larger than most other proteases.

Scientists don't know how this behemoth of an enzyme targets and degrades specific proteins — but it's good that the enzyme is so selective. If it degraded every protein it comes across, the cell would quickly die.

"We want to know how it's regulated, how it selects proteins to degrade, and how it cuts them apart," says Jap.

To help answer these questions, his team determined the changes the molecular machine undergoes as it readies itself for action. Using x-ray crystallography, they obtained an atomic-scale resolution structure of the molecular machine in its inactive state. This work was conducted at Berkeley Lab's Advanced Light Source, a national user facility that generates intense x-rays to probe the fundamental properties of substances.

They also developed a lower-resolution, three-dimensional map of the molecular machine in its activated state, meaning it's poised to snip apart a protein. This structure was determined using cryo-electron microscopy.

They then merged these two structures together, one dormant and the other ready to pounce on a protein.

"When we dock these structures, we can begin to ascertain the changes the enzyme undergoes as it transitions from an inactive to an active state," says Peter Walian, a scientist in Berkeley Lab's Life Sciences Division who also contributed to the research.

This first molecular-scale vantage of the enzyme in action offers insights into how it works. For example, the scientists found that only very small proteins can fit in the chamber the enzyme uses to break down proteins.

"This sheds light on how the enzyme targets specific proteins," says Jap.

They also learned more about how the enzyme uses a molecular ruler to mince proteins into pieces that only span three residues.

"This work is yielding valuable clues as to how the giant enzyme carries out very fundamental biological processes, with more insights to come," says Jap. "The obesity-related hormone is one of many interesting targets of the protease. There are likely other proteins and peptides, yet to be discovered, that are processed by this protease."

The research was supported by the National Institute of General Medical Sciences of the National Institutes of Health. The Advanced Light Source is supported by the Department of Energy's Office of Science.

Additional information:
The paper describing this work, titled, "Hybrid Molecular Structure of the Giant Protease Tripeptidyl Peptidase II," appears August 1, 2010 in an advance online publication of the journal Nature Structural & Molecular Biology.

####

About Lawrence Berkeley National Laboratory
Lawrence Berkeley National Laboratory provides solutions to the world’s most urgent scientific challenges including clean energy, climate change, human health, and a better understanding of matter and force in the universe. It is a world leader in improving our lives and knowledge of the world around us through innovative science, advanced computing, and technology that makes a difference. This content is solely the responsibility of Lawrence Berkeley National Laboratory. Berkeley Lab is a U.S. Department of Energy (DOE) national laboratory managed by the University of California for the DOE Office of Science.

For more information, please click here

Contacts:
Dan Krotz
(510) 486-4019

Copyright © Lawrence Berkeley National Laboratory

If you have a comment, please Contact us.

Issuers of news releases, not 7th Wave, Inc. or Nanotechnology Now, are solely responsible for the accuracy of the content.

Bookmark:
Delicious Digg Newsvine Google Yahoo Reddit Magnoliacom Furl Facebook

Related News Press

News and information

Radiation-guided nanoparticles zero in on metastatic cancer July 1st, 2016

Synthesized microporous 3-D graphene-like carbons: IBS research team create carbon synthesis using zeolites as a template July 1st, 2016

No need in supercomputers: Russian scientists suggest a PC to solve complex problems tens of times faster than with massive supercomputers June 30th, 2016

Surprising qualities of insulator ring surfaces: Surface phenomena in ring-shaped topological insulators are just as controllable as those in spheres made of the same material June 30th, 2016

Govt.-Legislation/Regulation/Funding/Policy

A drop of water as a model for the interplay of adhesion and stiction June 30th, 2016

How cancer cells spread and squeeze through tiny blood vessels (video) June 30th, 2016

Nanoscientists develop the 'ultimate discovery tool': Rapid discovery power is similar to what gene chips offer biology June 25th, 2016

Ultrathin, flat lens resolves chirality and color: Multifunctional lens could replace bulky, expensive machines June 25th, 2016

Possible Futures

Radiation-guided nanoparticles zero in on metastatic cancer July 1st, 2016

A drop of water as a model for the interplay of adhesion and stiction June 30th, 2016

No need in supercomputers: Russian scientists suggest a PC to solve complex problems tens of times faster than with massive supercomputers June 30th, 2016

Surprising qualities of insulator ring surfaces: Surface phenomena in ring-shaped topological insulators are just as controllable as those in spheres made of the same material June 30th, 2016

Academic/Education

JPK’s NanoWizard® AFM and ForceRobot® systems are being used in the field of medical diagnostics in the Supersensitive Molecular Layer Laboratory of POSTECH in Korea June 21st, 2016

Weizmann Institute of Science Presents: Weizmann Wonder Wander - 4G - is Online June 21st, 2016

NanoLabNL boosts quality of research facilities as Dutch Toekomstfonds invests firmly June 10th, 2016

The Institute for Transfusion Medicine at the University Hospital of Duisburg-Essen in Germany uses the ZetaView from Particle Metrix to quantify extracellular vesicles June 7th, 2016

Molecular Machines

Rice University's nanosubs gain better fluorescent properties for tracking June 17th, 2016

Little ANTs: Researchers build the world's tiniest engine May 3rd, 2016

Researchers create artificial protein to control assembly of buckyballs April 27th, 2016

Physicists build engine consisting of one atom: World's smallest heat engine uses just a single particle April 17th, 2016

Nanomedicine

Radiation-guided nanoparticles zero in on metastatic cancer July 1st, 2016

A drop of water as a model for the interplay of adhesion and stiction June 30th, 2016

How cancer cells spread and squeeze through tiny blood vessels (video) June 30th, 2016

Building a smart cardiac patch: 'Bionic' cardiac patch could one day monitor and respond to cardiac problems June 28th, 2016

Announcements

Radiation-guided nanoparticles zero in on metastatic cancer July 1st, 2016

Synthesized microporous 3-D graphene-like carbons: IBS research team create carbon synthesis using zeolites as a template July 1st, 2016

No need in supercomputers: Russian scientists suggest a PC to solve complex problems tens of times faster than with massive supercomputers June 30th, 2016

Surprising qualities of insulator ring surfaces: Surface phenomena in ring-shaped topological insulators are just as controllable as those in spheres made of the same material June 30th, 2016

Nanobiotechnology

Radiation-guided nanoparticles zero in on metastatic cancer July 1st, 2016

A drop of water as a model for the interplay of adhesion and stiction June 30th, 2016

How cancer cells spread and squeeze through tiny blood vessels (video) June 30th, 2016

Building a smart cardiac patch: 'Bionic' cardiac patch could one day monitor and respond to cardiac problems June 28th, 2016

Research partnerships

Superheroes are real: Ultrasensitive nonlinear metamaterials for data transfer June 25th, 2016

Soft decoupling of organic molecules on metal June 23rd, 2016

FEI and University of Liverpool Announce QEMSCAN Research Initiative: University of Liverpool will utilize FEI’s QEMSCAN technology to gain a better insight into oil and gas reserves & potentially change the approach to evaluating them June 22nd, 2016

Tailored DNA shifts electrons into the 'fast lane': DNA nanowire improved by altering sequences June 22nd, 2016

NanoNews-Digest
The latest news from around the world, FREE




  Premium Products
NanoNews-Custom
Only the news you want to read!
 Learn More
NanoTech-Transfer
University Technology Transfer & Patents
 Learn More
NanoStrategies
Full-service, expert consulting
 Learn More











ASP
Nanotechnology Now Featured Books




NNN

The Hunger Project







Car Brands
Buy website traffic