Skip to main content

Bacteria's protein quality control agent offers insight into origins of life

Our cells' process for transforming genes into useful proteins works much like an automobile factory's assembly line; there are schematics, parts, workers, motors, quality control systems and even recycling crews. If the cell's recycling process falters, abnormal protein fragments accumulate, potentially causing the cell's death. In nerve cells, the process is linked to a variety of neurodegenerative diseases, including ALS and dementia.
A new study from the lab of Claudio Joazeiro, PhD, published on line in the journal Cell on May 30, uncovers how simpler organisms -- bacteria and archaea -- manage the recycling of incomplete proteins. The discoveries not only offer new directions for fighting the virulence of some of humanity's most dangerous pathogens, including listeria, staph and streptococcus, they have implications for our understanding of how life itself evolved.
Joazeiro's group found the mechanism isn't so different from one they previously uncovered in plant, animal and fungal cells.
"We know that as cells are making proteins, this process is occasionally halted due to errors," says Joazeiro, who has joint appointments in the Scripps Research Department of Molecular Medicine in Jupiter, Florida, and the Center for Molecular Biology of Heidelberg University, in Germany.
"One of the problems with this is that the accumulation of partially formed proteins may be toxic. So in our lab, we're asking how do cells sense this, and how do they disassemble these proteins and recycle the building blocks?"
Organelles called ribosomes serve as the protein-assembly motors within cells. If they stall during the process of piecing together the parts -- amino acids -- cells have a variety of systems for responding. In human and other eukaryotic cells, when a ribosome jams, rescue factors split it open. A protein called Rqc2, also known as NEMF, zooms in and recruits another protein -- the ubiquitin ligase Ltn1, also called listerin. The Joazeiro lab previously discovered that Ltn1 marks the truncated protein fragment on ribosomes with a destruction tag called ubiquitin. Protease saws then handle the demolition.
Underscoring the importance of this recycling process, Joazeiro discovered in 2009 that mutations in Ltn1 can cause the death of nerve cells in mice, resulting in ALS-like symptoms. Bacteria have related, but somewhat more direct systems for addressing halted ribosomes and their protein fragments, according to the Cellreport. Studying the bacterium B. subtilis, the Joazeiro team found that Rqc2 itself marks the protein fragment with a flag -- a polymer made of the amino acid alanine. Thus flagged, proteases come to cut up the bad fragment.
Previous studies had suggested that in some pathogenic bacteria, Rqc2 proteins had a different job, one that functioned outside the cell, helping attach the microbes to hosts.
"We have found this is not the complete story," Joazeiro says. "Rqc2 plays a more fundamental role inside of bacterial cells."
The next step will be to find out whether the defective virulence of strep varieties lacking Rqc2 is primarily a consequence of their failure to recycle protein fragments inside the cell. As increasing varieties of pathogens develop multi-drug resistance to antibiotics, understanding bacterial virulence may prove especially necessary.
Equally important to Joazeiro is the realization that Rqc2 serves as a "living" molecular fossil, illuminating new insights about the ancient ancestral organism that emerged some 4 billion years ago to form the very base of the tree of life that evolved into the planet's biodiversity today.
"Shortly after cells invented how to make proteins, they were also faced with determining how to deal with incompletely made proteins," Joazeiro says. "The analyses suggest that an Rqc2 homolog in the last universal common ancestor already carried out this task."
In addition to lead author Joazeiro, the authors of the study, "Alanine Tails Signal Proteolysis in Bacterial Ribosome-Associated Quality Control," were Tina Mueller, George Tsaprailis and Christina Chiang of Scripps Research in Jupiter, Florida; Iryna Lytvyenko, Helge Paternoga, Anna Thrun and Simon Anders of Heidelberg University in Germany; Annika Balke and Christian Spahn of the Institute of Medical Physics and Biophysics in Berlin, Germany; Katja Nagler and Ilka Bischofs of Heidelberg University and the Max Planck Institute for Terrestrial Microbiology in Marburg, Germany, and Julie Maupin-Furlow of the University of Florida in Gainesville, Fla.
Story Source:
Materials provided by Scripps Research Institute. 
Note: Content may be edited.

Comments

Post a Comment

Popular posts from this blog

Dark matter may be older than the Big Bang

Dark matter, which researchers believe make up about 80% of the universe's mass, is one of the most elusive mysteries in modern physics. What exactly it is and how it came to be is a mystery, but a new Johns Hopkins University study now suggests that dark matter may have existed before the Big Bang. The study, published August 7 in  Physical Review Letters , presents a new idea of how dark matter was born and how to identify it with astronomical observations. "The study revealed a new connection between particle physics and astronomy. If dark matter consists of new particles that were born before the Big Bang, they affect the way galaxies are distributed in the sky in a unique way. This connection may be used to reveal their identity and make conclusions about the times before the Big Bang too," says Tommi Tenkanen, a postdoctoral fellow in Physics and Astronomy at the Johns Hopkins University and the study's author. While not much is known about its origins,...
Post a Comment
Read more

Organic laser diodes move from dream to reality

Researchers from Japan have demonstrated that a long-elusive kind of laser diode based on organic semiconductors is indeed possible, paving the way for the further expansion of lasers in applications such as biosensing, displays, healthcare, and optical communications. Long considered a holy grail in the area of light-emitting devices, organic laser diodes use carbon-based organic materials to emit light instead of the inorganic semiconductors, such as gallium arsenide and gallium nitride, used in traditional devices. The lasers are in many ways similar to organic light-emitting diodes (OLEDs), in which a thin layer of organic molecules emits light when electricity is applied. OLEDs have become a popular choice for smartphone displays because of their high efficiency and vibrant colors, which can easily be changed by designing new organic molecules. Organic laser diodes produce a much purer light enabling additional applications, but they require currents that are magnitudes h...
Post a Comment
Read more

Scientists challenge notion of binary sexuality with naming of new plant species

A collaborative team of scientists from the US and Australia has named a new plant species from the remote Outback. Bucknell University biology postdoctoral fellow Angela McDonnell and professor Chris Martine led the description of the plant that had confounded field biologists for decades because of the unusual fluidity of its flower form. The discovery, published in the open access journal  PhytoKeys , offers a powerful example of the diversity of sexual forms found among plants. The new species of bush tomato discovered in remote Australia provides a compelling example of the fact that sexuality among Earth's living creatures is far more diverse -- and interesting -- than many people likely realize. Bucknell University postdoctoral fellow Angela McDonnell and biology professor Chris Martine led the study following an expedition last year to relocate populations of the new plant, which were first noted by Australian botanists during the 1970s. Herbarium specimens from th...
Post a Comment
Read more