APR 18, 2017 05:36 PM PDT

Capturing the Transport of Cargo Into Cells

WRITTEN BY: Carmen Leitch
3 4 425

There are treatments for some viral infections and therapies for cancer, one group of such drugs is termed nucleoside analogs. While these drugs work, there is always room for improvement. New research has revealed the movement of a transporter getting these drugs into cells, which could improve drug development for serious illnesses. The work has been published in Nature, and the animation accompanying the work can be seen in the following video.

Nucleoside analogs work by interfering with the cellular machinery hijacked by cancer and viruses. They act like DNA building blocks and get incorporated into new genetic material, which is then compromised by these faulty parts.  Such drugs include AZT, a common HIV drug, 5-fluorouracil and gemcitabine, chemotherapy treatments, and acyclovir, a hepatitis B drug. 

The researchers found that one molecule is responsible for moving these nucleoside analogs and their normal counterparts into cells. That molecule, concentrative nucleoside transporter, or CNT, can be seen in the animation above slowly moving stuff like from one side of the cell and making periodic stops before reaching the other side of the cell membrane. 

"Our study is the first to provide a visualization of almost every possible conformation of this transporter in motion," said the senior author of the report, Seok-Yong Lee, Ph.D., an Associate Professor of Biochemistry at Duke University School of Medicine. "By understanding how this transporter recognizes and imports nucleosides, we may be able to redesign drugs that are better at getting inside specific cells like those harboring cancer or a virus."

The investigators used X-ray crystallography to understand more about how CNT transports nucleoside analogs and nucleotides - the bases of DNA that are required by cells for constructing genetic material (find out more about nucleoside and nucelotides from the video below). They thus obtained atomic level detail about the three-dimensional structure of the transporter protein, and did so as CNT changed shape while moving across the membrane. First the CNT captured a base on the cell surface, and after going through the motions, released it into the cell.

"We found that there is a region on the protein called the transport domain that acts like an elevator, shifting into different conformations as it transports cargo up and down across the membrane," said Lee. "Other studies had shown that many transporters move in this way, but ours is the first to record nearly all of the stages of the elevator model. This more detailed understanding could provide a platform to the future development of drugs that are more selective and efficient."

Lee noted that various transporters that import cargo like metabolites, ions, and neurotransmitters into the cell, have a mode of action that is similar to CNT. This new data could have not only aid in the development of treatments for viral infections and cancer; it may provide insight into other important physiological processes.

 

Sources: AAAS/Eurekalert! via Duke University, Nature

About the Author
  • Experienced research scientist and technical expert with authorships on 28 peer-reviewed publications, traveler to over 60 countries, published photographer and internationally-exhibited painter, volunteer trained in disaster-response, CPR and DV counseling.
You May Also Like
JUN 26, 2018
Health & Medicine
JUN 26, 2018
This Blood Test Can Tell if You Cheat on Your Diet
When a person ingests anything, be it food, drink or medication, it gets broken down in the bloodstream so that cells can absorb needed nutrients. When the
JUN 30, 2018
Immunology
JUN 30, 2018
CD4 T Cells Responsible for Inflammatory Bowel Disease
A specific subset of immune cells could be targeted to better treat inflammatory bowel disease (IBD). A new University of Alabama at Birmingham study point
JUN 30, 2018
Cell & Molecular Biology
JUN 30, 2018
Printable Bone Grafts may Change Therapeutics
An unlimited supply of materials for transplants like bone grafts would be a game-changer.
JUL 22, 2018
Cell & Molecular Biology
JUL 22, 2018
Using Nanosubmarines to Fight Tumors and Headaches
Researchers are getting closer to creating targeted therapies that are delivered directly where needed.
JUL 29, 2018
Microbiology
JUL 29, 2018
Revealing why Sepsis Causes Organs to Fail
The Staphylococcus aureus bacterium can cause devastating illnesses - called staph infections - and lead to organ failure.
AUG 08, 2018
Cell & Molecular Biology
AUG 08, 2018
Changing White Fat to Brown Fat
Not all fat is the same. Brown fat is thought to be fat healthier than white fat.
Loading Comments...