XML Feed for RxPG News   Add RxPG News Headlines to My Yahoo!   Javascript Syndication for RxPG News

Research Health World General
 
  Home
 
 Latest Research
 Cancer
 Psychiatry
 Genetics
 Surgery
 Aging
 Ophthalmology
 Gynaecology
 Neurosciences
 Pharmacology
 Cardiology
 Obstetrics
 Infectious Diseases
 Respiratory Medicine
 Pathology
 Endocrinology
 Immunology
 Nephrology
 Gastroenterology
 Biotechnology
  Drug Delivery
  Nanotechnology
 Radiology
 Dermatology
 Microbiology
 Haematology
 Dental
 ENT
 Environment
 Embryology
 Orthopedics
 Metabolism
 Anaethesia
 Paediatrics
 Public Health
 Urology
 Musculoskeletal
 Clinical Trials
 Physiology
 Biochemistry
 Cytology
 Traumatology
 Rheumatology
 
 Medical News
 Health
 Opinion
 Healthcare
 Professionals
 Launch
 Awards & Prizes
 
 Careers
 Medical
 Nursing
 Dental
 
 Special Topics
 Euthanasia
 Ethics
 Evolution
 Odd Medical News
 Feature
 
 World News
 Tsunami
 Epidemics
 Climate
 Business
Search

Last Updated: Aug 19th, 2006 - 22:18:38

Gang Lu, James M. Westbrooks, Amy L. Davidson and Jue Chen

Biotechnology Channel
subscribe to Biotechnology newsletter

Latest Research : Biotechnology

   DISCUSS   |   EMAIL   |   PRINT
ATP Hydrolysis is Required to Reset the ATP-binding Cassette Dimer
Dec 4, 2005, 09:48, Reviewed by: Dr.

"Many cancer cells are resistant to anticancer drugs because the ABC proteins are overabundant and get too good at pumping the drugs out before they can work,. Future therapies might exploit what we are finding out about these proteins' operation. It's too soon to talk about specific therapies, but because there are so many kinds of cancer out there, every piece of knowledge helps."

 
Scientists have a tough time visualizing the tiny hatchways that allow nutrients to pass into our cells, but a group of Purdue University biologists may have found the next best thing: a glimpse into the workings of the "motor" that opens and closes them.

A research team led by Jue Chen has clarified the connection between these minuscule gates – which are called membrane transport proteins – and the steps by which they use a cell's energy to permit or deny materials entry into the interior of the cell from the outside world.

In what the team perceives to be a three-step process, cells feed chemical energy to a tiny machine called an ABC protein, which is the part of the membrane protein that connects it to the interior of the cell. These ABC proteins use the energy to bend the membrane protein into its open and closed positions, allowing the cell both to bring in nutrients and to flush out waste.

"We think we have a better handle on a process fundamental to life in creatures from bacteria to humans," said Chen, who is an assistant professor of biology in Purdue's College of Science. "This is the first time the entire cycle has been visualized, and this could enhance our understanding of how the process of metabolism unfolds."

The team's paper appears in this week's issue of Proceedings of the National Academy of Sciences. Chen's group also includes her Purdue colleagues Gang Lu and James M. Westbrooks, as well as Amy L. Davidson, who recently relocated to Purdue from the Baylor College of Medicine. The team used X-ray crystallography and other advanced imaging techniques to obtain a clear picture of the ABC protein, a method which has only had limited success in revealing secrets of the membrane proteins themselves.

Membrane proteins in cells have been likened to spacecraft airlocks, which ensure that only the astronauts gain entry and no air is lost. Where spacecraft have metal walls, cells have membranes that surround their inner protoplasm, and their airlock proteins are highly complex individual molecules that allow nutrients to enter cells and waste products to leave them.

Of the thousands of membrane proteins that exist, scientists only know the structure of a few dozen. They are of great interest to biologists because, as the regulators of intercellular commerce, they essentially permit metabolism – and, thus, life itself – to continue. However, while most proteins dissolve in water and can be easily crystallized and examined, membrane proteins dissolve only in fatty substances, making it difficult to isolate them for study.

"If we had a better understanding of this class of proteins, we might know more about how our bodies use and transfer energy," Chen said. "It's an unfortunate gap in our knowledge of how living things work. But in this study, we looked at a protein that is a bit of a hybrid: one part of it is fat-soluble, and the other is water-soluble."

Because the entire membrane protein would not submit to crystallization, Chen's team focused their efforts on the ATP-binding cassette proteins, or ABC proteins for short, that connect the membrane proteins with the cell's interior. This portion of the protein is of the more study-friendly, water-soluble variety, and also plays a critical role in cellular commerce: It is the motor that drives a membrane protein's motion.

"We isolated the ABC proteins from an E. coli bacterium, which is a very common research subject," Chen said. "Different as these single-celled organisms are, their ABC proteins are structurally very similar to those in human cells, so studying them could help our knowledge of our own metabolism."

ABC proteins function like tiny tweezers and are powered by ATP, a chemical that animal cells use for energy. When ATP causes the tweezers to squeeze shut, the membrane proteins open to reveal a small cavity that can hold a nutrient or other substance the cell requires from the outside. Once the nutrient is in place, the cell uses water to break down the ATP, signaling the "tweezers" to relax, closing the membrane protein gate and capturing the nutrient. Lastly, the membrane protein releases the nutrient into the cell's interior.

"The ABC protein is like the inner door of the airlock; that's what we were able to see in operation in this study," Chen said. "If you opened both it and the membrane protein simultaneously, nothing would stop the interior of the cell from getting sucked out."

Chen admits that the team is not yet certain that the description of the process is complete, though it does seem compelling based on what science already knows about the workings of membrane proteins.

"We need to look closer at our information and try to find out more," Davidson said. "We will be applying several tests to our data in the near future to determine if our image of these proteins accurately describes their behavior."

This graphic illustrates the process by which a membrane protein opens and closes, as envisioned by Jue Chen's research team at Purdue University. ABC proteins, which are the inner portion of a membrane protein, function like tiny tweezers and are powered by ATP, a chemical that animal cells use for energy transport. When the tweezers squeeze shut, the outer section of the membrane protein opens to reveal a small cavity that can hold a nutrient or other substance the cell requires from the outside. Once the nutrient is there, the cell uses water to signal the "tweezers" to relax, closing the membrane protein gate and capturing the nutrient. Lastly, the membrane protein releases the nutrient into the cell's interior. (Purdue graphic/Chen labs)


Chen said the work might have long-term payoffs in the fight against cancer, though it was too soon to make more than general statements as to how.

"Many cancer cells are resistant to anticancer drugs because the ABC proteins are overabundant and get too good at pumping the drugs out before they can work," she said. "Future therapies might exploit what we are finding out about these proteins' operation. It's too soon to talk about specific therapies, but because there are so many kinds of cancer out there, every piece of knowledge helps."
 

- Proceedings of the National Academy of Sciences
 

www.purdue.edu

 
Subscribe to Biotechnology Newsletter
E-mail Address:

 

This research was sponsored in part by the National Institutes of Health and the Pew Charitable Trusts.

Members of Chen's research group are associated with the Purdue Cancer Center. One of just seven National Cancer Institute-designated basic-research facilities in the United States, the center attempts to help cancer patients by identifying new molecular targets and designing future agents and drugs for effectively detecting and treating cancer. The Cancer Center is part of the Oncological Sciences Center in Purdue's Discovery Park.


Related Biotechnology News

Gold Nanoparticle Molecular Ruler to Measure Smallest of Life’s Phenomena
Tiny inhaled particles take easy route from nose to brain
DNA Amplification and Detection Made Simple
Solitons Could Power Artificial Muscles
Nanoparticles could deliver multi-drug therapy to tumors
Nanotechnology can identify disease at early cellular level
Light-sensitive particles change chemistry at the flick of a switch
DNA Fragments for Making Tomatoes Taste Better Identified
'Custom' nanoparticles could improve cancer diagnosis and treatment
Human albumin from tobacco plants


For any corrections of factual information, to contact the editors or to send any medical news or health news press releases, use feedback form

Top of Page

 

© Copyright 2004 onwards by RxPG Medical Solutions Private Limited
Contact Us