Human acid-sensing ion channel 1a inhibition by snake toxin Mambalgin1

September 27, 2020

During the process of natural selection and evolution, many animals and plants, such as snakes, scorpions and sea anemones, have acquired the ability to produce venom, which is regarded as their strong weapon for self-defense and predation. Toxic peptides extracted from venom can specifically plays a key role in Acid-Sensing Ion Channel (ASIC), cell membrane surface receptors and proteins intensively involved in life activities. The interactions between venom and target proteins present the advantages of high specification and high affinity, in which venom has been treated as molecular tools to research in protein structures and their physiological functions for drug development.

On September 11th, 2020, a research group from University of Science and Technology of China, led by TIAN Changlin, in cooperation with LIU Lei's research group from Tsinghua University, initially resolved the hASIC1a and freeze electron structure of the compound of hASCI1a and Mambalgin1 through freeze electron microscopic technology. Also, the two research groups applied 19F-NMR and electrophysiological function analysis of patch clamp into use, uncovering the structural mechanism of polypeptide combination and hASIC1a inhibition. This result has been published on eLife with the title of "Structural Insights into Human Acid-sensing Ion Channel 1a Inhibition by Snake Toxin Mambalgin1".

In 2014, Tian Changlin Lab successfully produced Mambagin 1 venom and resolved its solution structure by NMR methods. However, it was still in question that how Mambalgin could specifically recognize and inhibit the mechanism of activity in human ASIC.

The compound structure of hASC1a/mambalgin1 shows that this kind of venom polypeptides are bonded to the outward of hASIC1a through electrostatic and hydrophobic interaction, having revised the former hypothesis of interaction between venom and ASIC. Further studies showed that Mambalgin1 selectively bonded closed ASCI and locked it in closed conformation. Even the concentration of protons elevates, ASIC can hardly switch to the open state. Therefore, the author put forwarded the concept of "closed-state trapping" mechanism, where Mambalgin1 could achieve ASIC activity inhibition. This would prepare the foundation for polypeptide medicine development.
-end-


University of Science and Technology of China

Related Technology Articles from Brightsurf:

December issue SLAS Technology features 'advances in technology to address COVID-19'
The December issue of SLAS Technology is a special collection featuring the cover article, ''Advances in Technology to Address COVID-19'' by editors Edward Kai-Hua Chow, Ph.D., (National University of Singapore), Pak Kin Wong, Ph.D., (The Pennsylvania State University, PA, USA) and Xianting Ding, Ph.D., (Shanghai Jiao Tong University, Shanghai, China).

October issue SLAS Technology now available
The October issue of SLAS Technology features the cover article, 'Role of Digital Microfl-uidics in Enabling Access to Laboratory Automation and Making Biology Programmable' by Varun B.

Robot technology for everyone or only for the average person?
Robot technology is being used more and more in health rehabilitation and in working life.

Novel biomarker technology for cancer diagnostics
A new way of identifying cancer biomarkers has been developed by researchers at Lund University in Sweden.

Technology innovation for neurology
TU Graz researcher Francesco Greco has developed ultra-light tattoo electrodes that are hardly noticeable on the skin and make long-term measurements of brain activity cheaper and easier.

April's SLAS Technology is now available
April's Edition of SLAS Technology Features Cover Article, 'CURATE.AI: Optimizing Personalized Medicine with Artificial Intelligence'.

Technology in higher education: learning with it instead of from it
Technology has shifted the way that professors teach students in higher education.

Post-lithium technology
Next-generation batteries will probably see the replacement of lithium ions by more abundant and environmentally benign alkali metal or multivalent ions.

Rethinking the role of technology in the classroom
Introducing tablets and laptops to the classroom has certain educational virtues, according to Annahita Ball, an assistant professor in the University at Buffalo School of Social Work, but her research suggests that tech has its limitations as well.

The science and technology of FAST
The Five hundred-meter Aperture Spherical radio Telescope (FAST), located in a radio quiet zone, with the targets (e.g., radio pulsars and neutron stars, galactic and extragalactic 21-cm HI emission).

Read More: Technology News and Technology Current Events
Brightsurf.com is a participant in the Amazon Services LLC Associates Program, an affiliate advertising program designed to provide a means for sites to earn advertising fees by advertising and linking to Amazon.com.