Nanotechnology Now







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

MIG Takes a Roll-Up-Your-Sleeves Approach with Revamped MEMS/Sensors Technical Event -- MIG welcomes technologists to MEMS Technical Congress, emphasizes working groups and breakout sessions on emerging MEMS & sensors, tech transfer and integration March 6th, 2015

Phenom-World announces the Phenom XL, world’s fastest desktop SEM to handle large samples March 6th, 2015

Air Bearing Stage / Systems Introduced by PI at Photonics West March 6th, 2015

Consistent Scalable Functionalised Graphene Capacity March 5th, 2015

Govt.-Legislation/Regulation/Funding/Policy

New research could lead to more efficient electrical energy storage March 4th, 2015

Energy-generating cloth could replace batteries in wearable devices March 4th, 2015

The taming of magnetic vortices: Unified theory for skyrmion-materials March 3rd, 2015

Black phosphorus is new 'wonder material' for improving optical communication March 3rd, 2015

Possible Futures

European roadmap for graphene science and technology published February 25th, 2015

Quantum research past, present and future for discussion at AAAS February 16th, 2015

World’s first compact rotary 3D printer-cum-scanner unveiled at AAAS by NTU Singapore start-up: With production funded by crowdsourcing, the first unit will be delivered to the United States in March February 16th, 2015

Nanotechnology Electric Vehicle (EV) Market Analysis Report 2015: According to Radiant Insights, Inc February 13th, 2015

Academic/Education

Get ready for NanoDays! March 5th, 2015

NanoTecNexus Launches New App for Learning About Nanotechnology—STEM Education Project Spearheaded by Interns February 26th, 2015

SUNY Poly CNSE Researchers and Corporate Partners to Present Forty Papers at Globally Recognized Lithography Conference: SUNY Poly CNSE Research Group Awarded Both ‘Best Research Paper’ and ‘Best Research Poster’ at SPIE Advanced Lithography 2015 forum February 25th, 2015

KIT Increases Commitment in Asia: DAAD Funds Two New Projects: Strategic Partnerships with Chinese Universities and Communi-cation Technologies Network February 22nd, 2015

Molecular Machines

Monitoring the real-time deformation of carbon nanocoils under axial loading February 18th, 2015

Stomach acid-powered micromotors get their first test in a living animal January 27th, 2015

Nanoshuttle wear and tear: It's the mileage, not the age January 26th, 2015

Mysteries of ‘Molecular Machines’ Revealed: Phenix software uses X-ray diffraction spots to produce 3-D image December 22nd, 2014

Nanomedicine

Patent for the Novel Cancer Therapies – Ceramide Nanoliposomes March 4th, 2015

Arrowhead to Present at 2015 Barclays Global Healthcare Conference March 4th, 2015

Democratizing synthetic biology: New method makes research cheaper, faster, and more accessible March 3rd, 2015

Pens filled with high-tech inks for do-it-yourself sensors March 3rd, 2015

Announcements

MIG Takes a Roll-Up-Your-Sleeves Approach with Revamped MEMS/Sensors Technical Event -- MIG welcomes technologists to MEMS Technical Congress, emphasizes working groups and breakout sessions on emerging MEMS & sensors, tech transfer and integration March 6th, 2015

Phenom-World announces the Phenom XL, world’s fastest desktop SEM to handle large samples March 6th, 2015

Air Bearing Stage / Systems Introduced by PI at Photonics West March 6th, 2015

Get ready for NanoDays! March 5th, 2015

Nanobiotechnology

Experiment and theory unite at last in debate over microbial nanowires: New model and experiments settle debate over metallic-like conductivity of microbial nanowires in bacterium March 4th, 2015

Untangling DNA with a droplet of water, a pipet and a polymer: With the 'rolling droplet technique,' a DNA-injected water droplet rolls like a ball over a platelet, sticking the DNA to the plate surface February 27th, 2015

Bacteria network for food: Bacteria connect to each other and exchange nutrients February 23rd, 2015

Building tailor-made DNA nanotubes step by step: New, block-by-block assembly method could pave way for applications in opto-electronics, drug delivery February 23rd, 2015

Research partnerships

French Institutes IRT Nanoelec and CMP Team up to Offer World’s First Service for Post-process 3D Technologies on Multi-Project-Wafer March 5th, 2015

New research could lead to more efficient electrical energy storage March 4th, 2015

Cambrios and Heraeus Jointly Create New, High-Conductivity Transparent Conductors: Two Companies' Combined Products Dramatically Extend Flexible Substrate Capabilities for Next-Generation Mass-Market Technology Products March 3rd, 2015

The taming of magnetic vortices: Unified theory for skyrmion-materials March 3rd, 2015

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 1999-2015 7th Wave, Inc. All Rights Reserved PRIVACY POLICY :: CONTACT US :: STATS :: SITE MAP :: ADVERTISE