(AGENPARL) – ven 02 agosto 2024 *Source*: Tokyo Institute of Technology
*Immediate release:* August 2, 2024
*Headline*: Conformational dynamics and allostery elucidate how GPCR couple
to multiple G-proteins, offering mechanistic insights into
coupling-promiscuity and novel drug discovery strategies
*(Tokyo, August 2)* In a groundbreaking study, a multinational research
team led by Dr. Adnan Sljoka (RIKEN) and Prof. Akio Kitao (Tokyo Tech), in
collaboration with Prof. Scott Prosser (University of Toronto), has carried
out experimental and computational studies to elucidate the mechanisms
behind G protein selectivity and efficacy in the human adenosine A2A
receptor (A2AR). A2AR is a member of major drug targets G protein-coupled
receptor (GPCR) superfamily, which engages the G protein and initiates cell
signaling, influencing heart health, inflammation, cancer, and brain
diseases. Scientists have made a breakthrough in understanding how A2AR can
engage and activate multiple binding G-proteins and the mechanisms of this
selective coupling. The research team discovered that the hallmark coupling
promiscuity in A2AR is a direct consequence of changes in activation
conformations. Moreover, the long-range (allosteric) communication
mechanisms elegantly control the sampling of specific conformers within a
dynamic conformational ensemble. This study offers profound insights into
GPCRs selectivity and biased signaling. These findings are expected to have
major implications in drug discovery and pave the way for novel
GPCR-targeted therapeutic strategies in treating various human conditions,
including cancer and neurogenerative disorders. This research will also
enable the design of more generalized computational and AI-driven studies,
pushing the boundaries in GPCR activation mechanisms and next-generation
pharmacology.
For more information, please visit the Tokyo Tech news that we posted at
https://www.titech.ac.jp/english/news/2024/069646 or contact us.
*Contact: *Emiko Kawaguchi, Public Relations Department, Tokyo Institute
*About Tokyo Institute of Technology*
Tokyo Tech stands at the forefront of research and higher education as the
leading university for science and technology in Japan. Tokyo Tech
researchers excel in fields ranging from materials science to biology,
computer science, and physics. Founded in 1881, Tokyo Tech hosts over
10,000 undergraduate and graduate students per year, who develop into
scientific leaders and some of the most sought-after engineers in industry.
Embodying the Japanese philosophy of “monotsukuri,” meaning “technical
ingenuity and innovation,” the Tokyo Tech community strives to contribute
to society through high-impact research.
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*Institute o**f Science Tokyo (Science Tokyo)* will be established on
October 1, 2024, following the merger between Tokyo Medical and Dental
University (TMDU) and Tokyo Institute of Technology (Tokyo Tech), with the
mission of “Advancing science and human wellbeing to create value for and
with society.”
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