* . *
  • About
  • Advertise
  • Privacy & Policy
  • Contact
Saturday, May 10, 2025
Earth-News
  • Home
  • Business
  • Entertainment
    The Weeknd made the apocalypse sexy at his 2025 tour launch in Arizona – Yahoo

    The Weeknd Turns Up the Heat at His 2025 Tour Launch in Arizona!

    Flutter Entertainment eyes U.S. prediction markets amid growing interest – Sports Business Journal

    Flutter Entertainment Sets Its Sights on U.S. Prediction Markets as Interest Soars

    SXSW Rom-Com ‘I Really Love My Husband’ Acquired for U.S. Release – Variety

    Heartfelt Romance: ‘I Really Love My Husband’ Set to Captivate U.S. Audiences!

    Georgia Entertainment CEO says large-scale production is slowing down – Decaturish

    Georgia Entertainment CEO Warns of Slowdown in Large-Scale Productions

    Zugalu Entertainment Welcomes Crimson Herring Studios to Its Family!

    Fall 2025 TV Schedule: Your Guide to the Complete Lineup – Wyoming News Now

    Get Ready for Fall 2025: Your Ultimate Guide to the Exciting TV Lineup!

  • General
  • Health
  • News

    Cracking the Code: Why China’s Economic Challenges Aren’t Shaking Markets, Unlike America’s” – Bloomberg

    Trump’s Narrow Window to Spread the Truth About Harris

    Trump’s Narrow Window to Spread the Truth About Harris

    Israel-Gaza war live updates: Hamas leader Ismail Haniyeh assassinated in Iran, group says

    Israel-Gaza war live updates: Hamas leader Ismail Haniyeh assassinated in Iran, group says

    PAP Boss to Niger Delta Youths, Stay Away from the Protest

    PAP Boss to Niger Delta Youths, Stay Away from the Protest

    Court Restricts Protests In Lagos To Freedom, Peace Park

    Court Restricts Protests In Lagos To Freedom, Peace Park

    Fans React to Jazz Jennings’ Inspiring Weight Loss Journey

    Fans React to Jazz Jennings’ Inspiring Weight Loss Journey

    Trending Tags

    • Trump Inauguration
    • United Stated
    • White House
    • Market Stories
    • Election Results
  • Science
  • Sports
  • Technology
    Comings and goings: MPT hires VP of technology, NPR announces changes to Business Desk – Current – For people in public media

    Exciting Leadership Changes: MPT Welcomes New VP of Technology and NPR Revamps Business Desk!

    Harnessing emerging technologies to power a small business – The Oaklandside

    Unlocking Success: How Emerging Technologies Can Transform Your Small Business

    Artificial intelligence (AI) – The Guardian

    Unlocking the Future: How Artificial Intelligence is Transforming Our World

    Technology Innovation to Take Center Stage at The 2025 National Restaurant Association Show – Restaurant Technology News

    Get Ready for a Tech Revolution: The 2025 National Restaurant Association Show Unveils Cutting-Edge Innovations!

    Newmont signs deal to use Chrysos Corporation technology – Capital Brief

    Newmont Partners with Chrysos Corporation to Revolutionize Mining Technology

    Air Force Invests in Whisper’s Ultraquiet Propulsion Technology – FLYING Magazine

    Air Force Invests in Whisper’s Ultraquiet Propulsion Technology – FLYING Magazine

    Trending Tags

    • Nintendo Switch
    • CES 2017
    • Playstation 4 Pro
    • Mark Zuckerberg
No Result
View All Result
  • Home
  • Business
  • Entertainment
    The Weeknd made the apocalypse sexy at his 2025 tour launch in Arizona – Yahoo

    The Weeknd Turns Up the Heat at His 2025 Tour Launch in Arizona!

    Flutter Entertainment eyes U.S. prediction markets amid growing interest – Sports Business Journal

    Flutter Entertainment Sets Its Sights on U.S. Prediction Markets as Interest Soars

    SXSW Rom-Com ‘I Really Love My Husband’ Acquired for U.S. Release – Variety

    Heartfelt Romance: ‘I Really Love My Husband’ Set to Captivate U.S. Audiences!

    Georgia Entertainment CEO says large-scale production is slowing down – Decaturish

    Georgia Entertainment CEO Warns of Slowdown in Large-Scale Productions

    Zugalu Entertainment Welcomes Crimson Herring Studios to Its Family!

    Fall 2025 TV Schedule: Your Guide to the Complete Lineup – Wyoming News Now

    Get Ready for Fall 2025: Your Ultimate Guide to the Exciting TV Lineup!

  • General
  • Health
  • News

    Cracking the Code: Why China’s Economic Challenges Aren’t Shaking Markets, Unlike America’s” – Bloomberg

    Trump’s Narrow Window to Spread the Truth About Harris

    Trump’s Narrow Window to Spread the Truth About Harris

    Israel-Gaza war live updates: Hamas leader Ismail Haniyeh assassinated in Iran, group says

    Israel-Gaza war live updates: Hamas leader Ismail Haniyeh assassinated in Iran, group says

    PAP Boss to Niger Delta Youths, Stay Away from the Protest

    PAP Boss to Niger Delta Youths, Stay Away from the Protest

    Court Restricts Protests In Lagos To Freedom, Peace Park

    Court Restricts Protests In Lagos To Freedom, Peace Park

    Fans React to Jazz Jennings’ Inspiring Weight Loss Journey

    Fans React to Jazz Jennings’ Inspiring Weight Loss Journey

    Trending Tags

    • Trump Inauguration
    • United Stated
    • White House
    • Market Stories
    • Election Results
  • Science
  • Sports
  • Technology
    Comings and goings: MPT hires VP of technology, NPR announces changes to Business Desk – Current – For people in public media

    Exciting Leadership Changes: MPT Welcomes New VP of Technology and NPR Revamps Business Desk!

    Harnessing emerging technologies to power a small business – The Oaklandside

    Unlocking Success: How Emerging Technologies Can Transform Your Small Business

    Artificial intelligence (AI) – The Guardian

    Unlocking the Future: How Artificial Intelligence is Transforming Our World

    Technology Innovation to Take Center Stage at The 2025 National Restaurant Association Show – Restaurant Technology News

    Get Ready for a Tech Revolution: The 2025 National Restaurant Association Show Unveils Cutting-Edge Innovations!

    Newmont signs deal to use Chrysos Corporation technology – Capital Brief

    Newmont Partners with Chrysos Corporation to Revolutionize Mining Technology

    Air Force Invests in Whisper’s Ultraquiet Propulsion Technology – FLYING Magazine

    Air Force Invests in Whisper’s Ultraquiet Propulsion Technology – FLYING Magazine

    Trending Tags

    • Nintendo Switch
    • CES 2017
    • Playstation 4 Pro
    • Mark Zuckerberg
No Result
View All Result
Earth-News
No Result
View All Result
Home Science

Repurposed protease controls important signaling molecule-activating protein

May 22, 2024
in Science
Repurposed protease controls important signaling molecule-activating protein
Share on FacebookShare on Twitter

Repurposed protease controls important signaling molecule-activating protein

Through protein structures obtained using cryo-electron microscopy, Chia-Hsueh Lee, Ph.D., St. Jude Department of Structural Biology demonstrated the role of the “pseudoprotease” iRhom2 in regulating the lifecycle of ADAM17, an important signaling molecule activator. Credit: St. Jude Children’s Research Hospital

Efficient communication between cells is vital for many biological processes, such as recruiting immune cells to combat disease. The rapid release of at least 80 signaling molecules, including tumor necrosis factor and epidermal growth factor, is controlled by a membrane-bound protease called ADAM17.

This process involves ADAM17 cleaving (shedding) the signaling molecules from their precursor forms in the membrane of a cell. The “pseudoprotease” iRhom2 aids in the maturation and transport of ADAM17. A lack of structural insight, however, has left the mechanisms underlying this process unclear.

Published today in Molecular Cell, scientists from St. Jude Children’s Research Hospital and the University of Oxford have used cryo-electron microscopy to reveal a series of structures of the human ADAM17/iRhom2 complex in both the active and inactive states. These structures show that iRhom2 acts as a gatekeeper to the ADAM17 lifecycle, interacting with key regions of ADAM17 that control its activity.

The work also offers potential avenues for drug design to combat diseases of chronic inflammation and autoimmune dysregulation. “We think there is potential to design small molecules that target iRhom2 instead of ADAM17 directly, or the interface between iRhom2 and ADAM17,” said co-corresponding author, Chia-Hsueh Lee, Ph.D., St. Jude Department of Structural Biology.

Defunct protease finds a new lease on life

iRhom2 is a pseudoprotease: It has all the structural features of a protease from the rhomboid family, except it lacks the protease-defining ability to cleave proteins. However, like an old dog learning new tricks, iRhom2 plays new-found roles in the scaffolding and transport of ADAM17.

As structural studies revealed, iRhom2’s impact on ADAM17 function starts during the initial synthesis of the two proteins. “The endoplasmic reticulum is where ADAM17 and iRhom2 are made, and at this stage, they form a complex,” explained Lee. iRhom2 then facilitates shuttling of ADAM17 to the Golgi apparatus for maturation, where the previous concept of iRhom2 serving merely as a “passive scaffold” was put to the test by Lee’s structures.

Repurposed protease controls important signaling molecule-activating protein

Graphical abstract. Credit: Molecular Cell (2024). DOI: 10.1016/j.molcel.2024.04.025

The interaction between iRhom2 and ADAM17 was presumed to occur exclusively between the proteins’ transmembrane domains, which pin the proteins to the cell membrane. To the researchers’ surprise, the two proteins also interact through their extracellular regions. Through those interactions, iRhom2 holds onto an important region of ADAM17 called the prodomain. The prodomain is a region that acts as a safety pin on a fire extinguisher.

“ADAM17 itself is self-inhibited. It has a prodomain cap to block its own protease site,” explained Lee.

iRhom2 helps pop the cap on ADAM17 activity

Within the Golgi apparatus, this self-regulating prodomain cap is cleaved. However, iRhom2 retains the ADAM17 cap until the complex reaches the cell membrane. This step is crucial to prevent the premature activation of ADAM17. The new structures reveal that once the cap is removed, ADAM17 is activated. This activation is marked by a significant gain in flexibility, which allows ADAM17 to search its surrounding space for substrates.

ADAM17 has been shown to play a role in the development and progression of multiple cancer types; however, the ADAM family of proteins is well conserved. A drug which targets ADAM17 can lead to off-target effects. Lee is optimistic that the structures can offer a blueprint for drug design ingenuity.

“Based on our model, if we could hold these two proteins together, for example, through a binder that enhances the interaction between iRhom2 and ADAM17, then iRhom2 will not release the prodomain cap,” said Lee. “This will significantly reduce ADAM17 activity.”

The study’s first authors are Fangfang Lu, University of Oxford and Hongtu Zhao, St. Jude. The study’s other co-corresponding authors are Hongtu Zhao, St. Jude and Matthew Freeman, University of Oxford. The study’s additional authors are Yaxin Dai and Yingdi Wang, St. Jude.

More information:
Fangfang Lu et al, Cryo-EM reveals that iRhom2 restrains ADAM17 protease activity to control the release of growth factor and inflammatory signals, Molecular Cell (2024). DOI: 10.1016/j.molcel.2024.04.025

Citation:
Repurposed protease controls important signaling molecule-activating protein (2024, May 22)
retrieved 22 May 2024
from https://phys.org/news/2024-05-repurposed-protease-important-molecule-protein.html

This document is subject to copyright. Apart from any fair dealing for the purpose of private study or research, no
part may be reproduced without the written permission. The content is provided for information purposes only.

>>> Read full article>>>
Copyright for syndicated content belongs to the linked Source : Phys.org – https://phys.org/news/2024-05-repurposed-protease-important-molecule-protein.html

Tags: proteaseRepurposedscience
Previous Post

Their financial aid was in limbo. What did these students decide about college?

Next Post

West Coast seabird study shows how they might one day share the air with wind turbines

Coupling coordination development of water resources-economy-ecology system in Shanxi Province based on system dynamics – Nature

Coupling coordination development of water resources-economy-ecology system in Shanxi Province based on system dynamics – Nature

May 10, 2025
Yolk’s on you – eggs break less when they land sideways – theregister.com

Egg-cellent Discovery: Why Eggs Break Less When They Land on Their Side!

May 10, 2025
How Science and Culture Are Under Attack—and What We Can Do About It – Greater Good: The Science of a Meaningful Life

Defending Science and Culture: Strategies for a Resilient Future

May 10, 2025
Lifestyle choices can help keep memory exercised, functioning – St. Louis Jewish Light

Boost Your Memory: How Lifestyle Choices Can Enhance Brain Function!

May 10, 2025
2025 IIHF Men’s World Championship Preview – NHL.com

Get Ready for the Thrills: A Sneak Peek at the 2025 IIHF Men’s World Championship!

May 10, 2025
Germany’s new economy boss has a plan — and it starts with risk, speed and big bets – CNBC

Germany’s New Economy Chief Unveils Bold Strategy: Embracing Risk, Speed, and Ambitious Investments!

May 10, 2025
The Weeknd made the apocalypse sexy at his 2025 tour launch in Arizona – Yahoo

The Weeknd Turns Up the Heat at His 2025 Tour Launch in Arizona!

May 10, 2025
‘Alias’ Actor Is Unrecognizable After Unexpected Health Diagnosis – parade.com

Shocking Transformation: ‘Alias’ Actor Unrecognizable After Surprising Health Diagnosis!

May 10, 2025
Opinion | The Politics of Medicaid Reform – WSJ

Navigating the Complex Landscape of Medicaid Reform: A Critical Perspective

May 10, 2025
Comings and goings: MPT hires VP of technology, NPR announces changes to Business Desk – Current – For people in public media

Exciting Leadership Changes: MPT Welcomes New VP of Technology and NPR Revamps Business Desk!

May 10, 2025

Categories

Archives

May 2025
MTWTFSS
 1234
567891011
12131415161718
19202122232425
262728293031 
« Apr    
Earth-News.info

The Earth News is an independent English-language daily published Website from all around the World News

Browse by Category

  • Business (20,132)
  • Ecology (598)
  • Economy (609)
  • Entertainment (21,522)
  • General (15,210)
  • Health (9,651)
  • Lifestyle (614)
  • News (22,149)
  • People (612)
  • Politics (616)
  • Science (15,831)
  • Sports (21,119)
  • Technology (15,599)
  • World (599)

Recent News

Coupling coordination development of water resources-economy-ecology system in Shanxi Province based on system dynamics – Nature

Coupling coordination development of water resources-economy-ecology system in Shanxi Province based on system dynamics – Nature

May 10, 2025
Yolk’s on you – eggs break less when they land sideways – theregister.com

Egg-cellent Discovery: Why Eggs Break Less When They Land on Their Side!

May 10, 2025
  • About
  • Advertise
  • Privacy & Policy
  • Contact

© 2023 earth-news.info

No Result
View All Result

© 2023 earth-news.info

No Result
View All Result

© 2023 earth-news.info

Go to mobile version