When ribosomes collide: How bacteria clean up after molecular crashes
Date:
March 9, 2022
Source:
Howard Hughes Medical Institute
Summary:
Tiny cellular machines called ribosomes build proteins. When
this building process goes awry in bacteria, ribosomes collide,
triggering the arrival of a first responder molecule that begins
a rescue operation.
FULL STORY ==========================================================================
The knobby, 3D structure on the screen in front of Rachel Green showed
an intracellular car wreck never before seen by scientists. It also
confirmed a hypothesis a team in her lab had been working on for months.
==========================================================================
But at first, Green wasn't so impressed. "That's it?" she remembers
thinking wryly.
It was early 2021, and she was on sabbatical, working at Ludwig
Maximilian University of Munich with her friend and collaborator, Roland Beckmann. Green, a Howard Hughes Medical Institute Investigator at Johns Hopkins University, had told him about a project in her lab exploring a long-standing biological mystery. They were trying to fill in a key gap
in scientists' knowledge about how bacterial cells respond to protein
synthesis problems. Because cells need proteins for nearly everything
they do, this response is critical for normal function.
Green's team had a good idea of what was going on, but they didn't
have the snapshots to prove it. Beckmann, a structural biologist,
was intrigued. Using a technique called cryo-electron microscopy, his
team revealed what happens at the scene -- that is, if you knew what to
look for.
"When they first show you a structure, you can't really tell what
anything is because everything's gray," Green says. "Roland pointed to
some little blob, and said, 'Look, there it is!'" Her team suspected
that the "little blob" acted as a molecular first responder that shows
up at the accident. Beckmann's images confirmed the molecule's identity
and presented new intel about how this rescue operation, a method of
quality control for bacteria, works. Beckmann, Green, and a group of
scientists in her lab led by Allen Buskirk first described the research
in a preprint on bioRxiv.org and later in the journal NatureonMarch 9,
2022. The work could offer clues about how other, more complex organisms
-- perhaps even humans - - keep protein production on track.
========================================================================== Molecular machines known as ribosomes quite literally follow instructions encoded in a linear strand of genetic material. As they travel along
the strand, they build a protein. Sometimes, though, this machinery malfunctions.
Earlier research in yeast, whose cells resemble those of animals,
had shown that ribosomes stall when they get into trouble. Like a
car that stops too suddenly, a stalled ribosome can be rear-ended
by the one behind it. Green's lab had previously identified a yeast
molecule that responds to these collisions. Like a tiny Jaws of Life,
the molecule cuts the stalled ribosome free. It's the first step in
a rescue effort that ultimately lets the cell salvage and reuse these
valuable, protein-making machines.
Bacterial cells' ribosomes can get jammed up too, but scientists doubted
that bacteria respond to collisions the same way yeast do. That's because researchers already knew that bacteria have their own distinct method for rescuing wrecked ribosomes, says Jamie Cate, a biochemist and structural biologist at the University of California, Berkeley, who was not involved
in the project.
No one knew exactly what kicked off the bacterial rescue effort, but
they expected that it would be something entirely different from yeast,
Cate says.
Instead, the new research suggests that both bacteria and yeast initiate
this process the same way -- by summoning blade-like first responders.
"The cool thing is that both molecules recognize ribosomes that have
collided into each other," Cate says.
In Green's lab in Baltimore, Buskirk and first author Kazuki Saito
identified the first responder in bacteria as a molecule called SmrB
and explored how it carried out its job. Beckmann's structure "was the
final piece of the puzzle," Buskirk says.
Beckmann's group captured the first-ever images of a collision between two bacterial ribosomes, then color-coded them so their components weren't
lost in a sea of gray. After adding SmrB to the sample containing the ribosomes, the team saw the molecule appear at the center of the crash.
Biochemical experiments revealed that SmrB, like its yeast counterpart,
cuts the wrecked ribosomes apart. And not only do the two molecules
share a job description, bacterial SmrB and its yeast counterpart are
also close relatives, the team found. Researchers haven't yet been able
to visualize how the yeast version interacts with ribosomes during
a collision. So, the similar but simpler SmrB may give scientists a
foothold for understanding how the process works in other organisms.
"Everything else about these rescue pathways is very different,"
Green says.
"We didn't anticipate we would find an aspect that appears to be
universal."
========================================================================== Story Source: Materials provided by Howard_Hughes_Medical_Institute. Note: Content may be edited for style and length.
========================================================================== Journal Reference:
1. Kazuki Saito, Hanna Kratzat, Annabelle Campbell, Robert Buschauer,
A.
Maxwell Burroughs, Otto Berninghausen, L. Aravind, Rachel Green,
Roland Beckmann, Allen R. Buskirk. Ribosome collisions induce
mRNA cleavage and ribosome rescue in bacteria. Nature, 2022; DOI:
10.1038/s41586-022-04416- 7 ==========================================================================
Link to news story:
https://www.sciencedaily.com/releases/2022/03/220309111042.htm
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