Nav: Home

Study reveals the protein structure of the human apoptosome

October 04, 2016

(Boston)--Programmed cell death, or apoptosis, plays a central role in the maintenance of human health by providing a line of defense against unrestricted cell growth that occurs in many cancers and AIDS as well as in neurodegenerative diseases and stroke.

Researchers from Boston University School of Medicine (BUSM) have for the first time mapped an active human apoptosome. This model, which appears online in the journal eLife, helps provide a better understanding of how cell death occurs and may lead to treatment options to either enhance or suppress this process.

Between 50-70 billion human cells commit suicide each day as a result of environmental stress or developmental cues. Damaged or unwanted cells undergo a process during which they are removed in a controlled manner and the resulting cellular components may be recycled.

Cellular signaling in the programmed death pathway culminates in a complex assembly of proteins termed the "apoptosome." This large wheel-like structure recruits and activates specific proteases (enzymes that split proteins) to dismantle proteins in the cytoplasm and the nucleus. Thus, the cell is broken down into pieces from the inside by this "wheel of death."

The research team, led by Christopher W. Akey, PhD, BUSM professor of physiology & biophysics, determined the near atomic structure of the apoptosome using cryo-electron microscopy and were able to build a three-dimensional model.

According to the researchers the apoptosome is a wheel-like structure with seven spokes. On top of the wheel is a spiral-shaped disk formed by protease docking, while active domains of the proteases are flexibly-tethered to the disk. When active the apoptosome is a dynamic molecular machine with three to five protease molecules tethered to it at any given time. The number of proteolytic units parked on the wheel could vary, resulting in a changing level of dismantling activity. A soluble protease is in turn cleaved and activated by the active apoptosome and this soluble protease then targets cellular components.

"This study helps us to better understand the fundamentals of a critical system in the body that helps regulate tissue development and stability. Our hope is to find drugs to target this wheel of death to either enhances or suppress its function," said Akey.
-end-
Funding for this study was provided by the National Institutes of Health.

Boston University Medical Center

Related Neurodegenerative Diseases Articles:

Study suggests a protein could play key role in neurodegenerative diseases
Research led by Queen Mary University of London and the University of Seville around one protein's role in regulating brain inflammation could improve our understanding of neurodegenerative diseases.
Beyond finding a gene: Same repeated stretch of DNA in three neurodegenerative diseases
Four different rare diseases are all caused by the same short segment of DNA repeated too many times, a mutation researchers call noncoding expanded tandem repeats.
Protein complex may help prevent neurodegenerative diseases
The protein complex NAC in the cell helps to prevent the aggregration of proteins associated with several neurodegenerative diseases.
Experimental Biology highlights -- Cancer, neurodegenerative diseases and medical news
Embargoed press materials are now available for the Experimental Biology (EB) 2019 meeting, to be held in Orlando April 6-9.
Circadian clock plays unexpected role in neurodegenerative diseases
Northwestern University researchers induced jet lag in a fruit fly model of Huntington disease and found that jet lag protected the flies' neurons.
Neurodegenerative diseases identified using artificial intelligence
Researchers have developed an artificial intelligence platform to detect a range of neurodegenerative disease in human brain tissue samples, including Alzheimer's disease and chronic traumatic encephalopathy.
Open-science model for drug discovery expands to neurodegenerative diseases
Parkinson's disease and Amyotrophic Lateral Sclerosis are the newest frontiers for open science drug discovery, a global movement led by academic scientists in Toronto that puts knowledge sharing and medication affordability ahead of patents and profits.
New stage in the development of corrective mechanisms for ischemia and neurodegenerative diseases
In the last decade, there has been a growing body of experimental data confirming that neural networks are the minimal functional unit of the nervous system.
Scientists from TU Dresden search for new methods to cure neurodegenerative diseases
Behavioural experiments confirm: Additional neurons improve brain function.
Using graphene to detect ALS, other neurodegenerative diseases
Graphene can determine whether cerebrospinal fluid comes from a person with ALS, MS or from someone without a neurodegenerative disease.
More Neurodegenerative Diseases News and Neurodegenerative Diseases Current Events

Best Science Podcasts 2019

We have hand picked the best science podcasts for 2019. Sit back and enjoy new science podcasts updated daily from your favorite science news services and scientists.
Now Playing: TED Radio Hour

Rethinking Anger
Anger is universal and complex: it can be quiet, festering, justified, vengeful, and destructive. This hour, TED speakers explore the many sides of anger, why we need it, and who's allowed to feel it. Guests include psychologists Ryan Martin and Russell Kolts, writer Soraya Chemaly, former talk radio host Lisa Fritsch, and business professor Dan Moshavi.
Now Playing: Science for the People

#538 Nobels and Astrophysics
This week we start with this year's physics Nobel Prize awarded to Jim Peebles, Michel Mayor, and Didier Queloz and finish with a discussion of the Nobel Prizes as a way to award and highlight important science. Are they still relevant? When science breakthroughs are built on the backs of hundreds -- and sometimes thousands -- of people's hard work, how do you pick just three to highlight? Join host Rachelle Saunders and astrophysicist, author, and science communicator Ethan Siegel for their chat about astrophysics and Nobel Prizes.