Illuminating a biological light switch
Date:
January 26, 2022
Source:
Weill Cornell Medicine
Summary:
Using an innovative new imaging technique, researchers have revealed
the inner workings of a family of light-sensing molecules in
unprecedented detail and speed. The work could inform new strategies
in the burgeoning field of optogenetics, which uses light pulses
to alter the activity of individual neurons and other cells.
FULL STORY ========================================================================== Using an innovative new imaging technique, researchers at Weill Cornell Medicine have revealed the inner workings of a family of light-sensing molecules in unprecedented detail and speed. The work could inform new strategies in the burgeoning field of optogenetics, which uses light
pulses to alter the activity of individual neurons and other cells.
========================================================================== Light-sensitive proteins drive many crucial processes in biology,
ranging from photosynthesis to vision. Much of the science community's understanding of these proteins comes from studies on bacteriorhodopsin,
a protein responsible for photosynthesis in certain single-celled
organisms. Researchers have previously solved the three-dimensional
structure of bacteriorhodopsin and studied its activity in detail,
but the limitations of available techniques left puzzling gaps in the
resulting models.
The new study, published Dec. 10 in Nature Communications, describes a technique developed by the investigators, called line-scanning high-speed atomic force microscopy, that captures the motions of bacteriorhodopsin
in response to light on a millisecond time scale.
"The solution of protein structures has become quite straightforward,"
said senior author Dr. Simon Scheuring, professor of physiology and
biophysics in anesthesiology at Weill Cornell Medicine. "But a current challenge is to assess kinetics, which provide a dynamic understanding
of the system." In particular, other methods that track the activity
of individual molecules operate too slowly to reveal how the protein
changes shape over short time periods, as bacteriorhodopsin appears to
do in response to light. Dr. Scheuring compares these techniques to a
movie camera with a slow shutter, which might capture a fast-moving bird
at one side of the screen and then the other but be unable to track it
in between those two points.
Previously, researchers have tackled that problem by handicapping the
bird: looking at variant forms of bacteriorhodopsin. "Up to now, to study
the kinetics of bacteriorhodopsin, people were using mutants that were
slower," said lead author Dr. Alma Perez Perrino, a postdoctoral fellow
in Dr.
Scheuring's laboratory. The slower variants don't represent the normal
activity of the protein, though. To address that, Dr. Perez Perrino and
her colleagues developed line-scanning high-speed atomic force microscopy, which sacrifices some image detail for a much faster frame rate, like
taking blurrier images of the bird in order to follow it all the way
across the screen.
"We are tracking the protein every 1.6 milliseconds, so we could explore
the speed of the wild-type bacteriorhodopsin," said Dr. Perez Perrino.
In response to light, bacteriorhodopsin switches between open and closed states. Using their faster imaging technique, the researchers discovered
that the transition to the open state and the duration of the open state
always happen at the same speed, but the molecule remains in the closed
state for longer periods as the intensity of the light decreases.
Optogenetics researchers insert genes for light-sensing molecules in
neurons or other cells, enabling them to change the cells' behavior with
light pulses.
That work has revolutionized neuroscience, and holds potential
for treating neurological diseases as well. The more researchers
know about light-sensing proteins, the further they'll be able
to push optogenetics. "Ultimately, you want to switch on a
process, then get the maximum out of it, and be able to switch
it off again immediately," said Dr. Scheuring. "So, it is very
important to know the kinetics of the molecules for that switching."
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Content may be edited for style and length.
========================================================================== Journal Reference:
1. Alma P. Perrino, Atsushi Miyagi, Simon Scheuring. Single molecule
kinetics of bacteriorhodopsin by HS-AFM. Nature Communications,
2021; 12 (1) DOI: 10.1038/s41467-021-27580-2 ==========================================================================
Link to news story:
https://www.sciencedaily.com/releases/2022/01/220126122509.htm
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