Nanotechnology Now

Our NanoNews Digest Sponsors



Heifer International

Wikipedia Affiliate Button


android tablet pc

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

Lifeboat Foundation Responds to Largest Ebola Outbreak in History October 2nd, 2014

Iran's Sharif University to Host 4th Conference on Nanostructured Solar Cells October 2nd, 2014

Multifunctional Cotton Fabrics Produced in Iran Using Nanotechnology October 2nd, 2014

Graphene chips are close to significant commercialization October 1st, 2014

Govt.-Legislation/Regulation/Funding/Policy

Platinum meets its match in quantum dots from coal: Rice University's cheap hybrid outperforms rare metal as fuel-cell catalyst October 1st, 2014

$18-million NSF investment aims to take flat materials to new heights: 2-D alternatives to graphene may enable exciting advances in electronics, photonics, sensors and other applications October 1st, 2014

Novel approach to magnetic measurements atom-by-atom October 1st, 2014

'Stealth' nanoparticles could improve cancer vaccines October 1st, 2014

Possible Futures

Lifeboat Foundation Responds to Largest Ebola Outbreak in History October 2nd, 2014

Air Force’s 30-year plan seeks 'strategic agility' August 1st, 2014

IBM Announces $3 Billion Research Initiative to Tackle Chip Grand Challenges for Cloud and Big Data Systems: Scientists and engineers to push limits of silicon technology to 7 nanometers and below and create post-silicon future July 10th, 2014

Virus structure inspires novel understanding of onion-like carbon nanoparticles April 10th, 2014

Academic/Education

Yale University and Leica Microsystems Partner to Establish Microscopy Center of Excellence: Yale Welcomes Scientists to Participate in Core Facility Opening and Super- Resolution Workshops October 20 Through 31, 2014 September 30th, 2014

Rice launches Center for Quantum Materials: RCQM will immerse global visitors in cross-disciplinary research September 30th, 2014

Biosensors Get a Boost from Graphene Partnership: $5 Million Investment Supports Dozens of Jobs and Development of 300mm Fabrication Process and Wafer Transfer Facility September 18th, 2014

Malvern technology delivers Malvern reliability in multi-disciplinary lab at Queen Mary University London September 9th, 2014

Molecular Machines

Optimum inertial design for self-propulsion: A new study investigates the effects of small but finite inertia on the propulsion of micro and nano-scale swimming machines July 29th, 2014

Breakthrough laser experiment reveals liquid-like motion of atoms in an ultra-cold cluster: University of Leicester research team unlocks insights into creation of new nano-materials July 25th, 2014

NIST shows ultrasonically propelled nanorods spin dizzyingly fast July 22nd, 2014

University of Illinois researchers demonstrate novel, tunable nanoantennas July 14th, 2014

Nanomedicine

Arrowhead Expands Management Team with Appointment of Susan Boynton as Vice President Global Regulatory Affairs October 1st, 2014

Nanobotmodels present metastasis and angiogenesis medical animation October 1st, 2014

'Stealth' nanoparticles could improve cancer vaccines October 1st, 2014

New Absorber Will Lead to Better Biosensor: Biosensors are more sensitive and able to detect smaller changes in the environment October 1st, 2014

Announcements

Lifeboat Foundation Responds to Largest Ebola Outbreak in History October 2nd, 2014

Iran's Sharif University to Host 4th Conference on Nanostructured Solar Cells October 2nd, 2014

Multifunctional Cotton Fabrics Produced in Iran Using Nanotechnology October 2nd, 2014

Graphene chips are close to significant commercialization October 1st, 2014

Nanobiotechnology

Ad-REIC vaccine: A magic bullet for cancer treatment September 30th, 2014

How things coil: Researchers discover that simulation technology designed for Hollywood can be used as a predictive tool for understanding fundamental engineering problems September 29th, 2014

Penn Team Studies Nanocrystals by Passing Them Through Tiny Pores September 26th, 2014

New NIH/DOE Grant for Life Science Studies at NSLS-II: Funding will support operation of three powerful experimental stations designed to reveal detailed structures of proteins, viruses, and more September 23rd, 2014

Research partnerships

Novel approach to magnetic measurements atom-by-atom October 1st, 2014

'Stealth' nanoparticles could improve cancer vaccines October 1st, 2014

Stressed Out: Research Sheds New Light on Why Rechargeable Batteries Fail October 1st, 2014

Research mimics brain cells to boost memory power September 30th, 2014

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







© Copyright 1999-2014 7th Wave, Inc. All Rights Reserved PRIVACY POLICY :: CONTACT US :: STATS :: SITE MAP :: ADVERTISE