Navigation Links
Scripps Research study reveals new activation mechanism for pain sensing channel

The researchers found that TRPA1, a protein that helps transmit pain signals, is a direct sensor of reactive chemicals. "While many noxious and pungent compounds were known to activate this pain receptor, we discovered that they do so by directly and irreversibly binding to the cysteine amino acids of this protein," said Ardem Patapoutian, a Scripps Research scientist whose laboratory conducted the study. "Our study shows that TRPA1 activation is directly linked to chemical insult."

"Cysteines, one of the twenty building blocks of all proteins, are known to undergo oxidation/reduction reactions," Patapoutian continued. "Somehow the TRPA1 protein is tuned to sense cysteine modifications. In fact, any cysteine reactive agent seems to activate TRPA1, although we don't know exactly how cysteine binding translates into ion channel activation."

But this activation mechanism comes with an interesting property.

"Generally, compounds that activate ion channels bind in a lock-and-key mechanism that is readily reversible," said Lindsey Macpherson, another author of the study and a Ph.D. candidate in the Scripps Research Kellogg School of Science and Technology. "The mechanism by which noxious compounds activate TRPA1 is unique. For example, compounds that activate an ion channels through a lock-and-key mechanism have structural similarity. TRPA1 activators have no structural similarity; instead, they share a common potential for chemical reactivity, and their binding is long-lasting."

TRPA1 is not unique among proteins to be activated by cysteine modifying agents, the study noted. Another signaling protein known as Kelch-like ECH-associated protein 1 (KEAP1) is activated by many of the same compounds that activate TRPA1; KEAP1 is a sensor for oxidative damage from free radicals and upregulates expression of antioxidant enzymes. Apparently, reactive compounds can activate at least two pathways through cysteine modification as a warning against cell damage, the study concluded.

"Our findings, which are the result of a successful collaboration with the Ben Cravatt and Peter Schultz labs at Scripps Research, show that modification of reactive cysteines within TRPA1 can cause channel activation," Macpherson said. "Our research efforts are now aimed at further understanding how binding of these compounds activate the channel, and identifying the physiological role of TRPA1 in sensing oxidative stress." The protein is currently being investigated by several pharmaceutical companies as a potential target for chronic pain, Patapoutian noted.
'"/>

Source:Scripps Research Institute


Related biology news :

1. Scripps scientists find potential for catastrophic shifts in Pacific ecosystems
2. To Stop Evolution: New Way Of Fighting Antibiotic Resistance Demonstrated By Scripps Scientists
3. Scripps research scientists identify infertility molecule
4. Scripps research scientists solve structure of a critical innate immune system protein
5. New Scripps Oceanography project to study sediments and ecosystem restoration in Venice lagoon
6. Scripps research team discovers a chemical pathway that causes mice to overeat and gain weight
7. Scripps research study reveals structural dynamics of single prion molecules
8. Scripps research study shows humans and plants share common regulatory pathway
9. Scripps research team sheds light on long-sought cold sensation gene
10. Researchers discover way to make cells in the eye sensitive to light
11. Quantum Dots Research Leads to New Knowledge about Protein Binding in Plants

Post Your Comments:
*Name:
*Comment:
*Email:


(Date:6/2/2016)... 2016 The Department of Transport Management ... 44 million US Dollar project, for the , ... Personalization, Enrolment, and IT Infrastructure , to ... and implementation of Identity Management Solutions. Numerous renowned international vendors ... Decatur was selected for the most compliant and ...
(Date:5/20/2016)... 20, 2016  VoiceIt is excited to announce ... By working together, VoiceIt and VoicePass ... and VoicePass take slightly different approaches to voice ... security and usability. ... new partnership. "This marketing and technology ...
(Date:4/28/2016)... BANGALORE, India , April 28, 2016 ... of Infosys (NYSE: INFY ), and Samsung SDS, ... partnership that will provide end customers with a more ... payment services.      (Logo: http://photos.prnewswire.com/prnh/20130122/589162 ) ... financial services, but it also plays a fundamental part in ...
Breaking Biology News(10 mins):
(Date:6/24/2016)... 2016 Epic Sciences unveiled a liquid ... to PARP inhibitors by targeting homologous recombination deficiency ... new test has already been incorporated into numerous ... types. Over 230 clinical trials are ... including PARP, ATM, ATR, DNA-PK and WEE-1. Drugs ...
(Date:6/23/2016)... ... June 23, 2016 , ... ... announce the launch of their brand, UP4™ Probiotics, into Target stores nationwide. The ... is proud to add Target to its list of well-respected retailers. This list ...
(Date:6/23/2016)... Houston Methodist Willowbrook Hospital has signed ... to serve as their official health care provider. ... will provide sponsorship support, athletic training services, and ... volunteers, athletes and families. "We are ... and to bring Houston Methodist quality services and ...
(Date:6/23/2016)... , June 23, 2016   EpiBiome , a ... $1 million in debt financing from Silicon Valley Bank ... automation and to advance its drug development efforts, as ... facility. "SVB has been an incredible strategic ... services a traditional bank would provide," said Dr. ...
Breaking Biology Technology: