Evidence of protein folding at site of intracellular droplets

Date:
February 19, 2021
Source:
University of Notre Dame
Summary:
Researchers have found that elevated concentrations of proteins
within the droplets triggered a folding event, increasing the
potential for protein aggregation -- or misfolding -- which has
been linked to neurological diseases including Alzheimer's disease
and amyotrophic lateral sclerosis (ALS).



FULL STORY ========================================================================== Scientists have discovered the first evidence of protein folding driven
by liquid-liquid phase separation, a phenomenon in which fluids form
into microscopic droplets and separate inside cells -- like drops of
oil in water.


==========================================================================
In a study published in the journal Chemical Science, researchers at the University of Notre Dame found that elevated concentrations of proteins
within the droplets triggered a folding event, increasing the potential
for protein aggregation -- or misfolding -- which has been linked to neurological diseases including Alzheimer's disease and amyotrophic
lateral sclerosis (ALS).

"These particular proteins are intrinsically disordered -- they have no
well- defined structure -- but when forced together by these droplets,
we see evidence of folding," said Arnaldo Serrano, assistant professor in
the Department of Chemistry and Biochemistry at Notre Dame and principal investigator of the study. Proteins are naturally shapeless, like pieces
of cooked spaghetti -- and only function when folded into specific, three dimensional structures. "Imagine you're in a crowd, and everyone in the
crowd has their arms stretched out. You're not going to fit together very
well. You pull your arms in, and maybe pull your hands together. When
it gets crowded, these proteins condense down into a folded structure."
Over the years, researchers have studied how the microscopic droplets,
forming naturally and spontaneously within cellular structures, serve
multiple functions. Cells can direct and contain dangerous biomaterial
within the fluid compartments to protect the cell from harm. There's
also evidence that they can drive various chemical reactions such as
protein aggregation.

In their study, Serrano and his team used infrared spectroscopy to measure
the folding of a specific protein associated with ALS. The infrared
lasers create pulses of light, generating vibrational frequencies that
act as an identifier similar to a fingerprint. The frequency uniquely
and accurately identifies a protein's structure as folded or unfolded.

While the research did not test for evidence of aggregation of
the proteins, Serrano explained protein folding and aggregation are
intimately linked.

"You can think of aggregation as a second-order folding event," he said.

"Proteins often fold into intermediate structures along the way towards aggregation. We've validated this idea that proteins in the droplet don't
have a lot of room and are forced to fold -- the next logical step is
they're forced to aggregate." Serrano said he and his team are currently conducting a follow-up study to determine whether such a folding event
could in fact serve as a first step for misfolding in other proteins.

========================================================================== Story Source: Materials provided by University_of_Notre_Dame. Original
written by Jessica Sieff. Note: Content may be edited for style and
length.


========================================================================== Journal Reference:
1. Dean N. Edun, Meredith R. Flanagan, Arnaldo L. Serrano. Does liquid-
liquid phase separation drive peptide folding? Chemical Science,
2021; DOI: 10.1039/D0SC04993J ==========================================================================

Link to news story: https://www.sciencedaily.com/releases/2021/02/210219155854.htm

--- up 9 weeks, 3 days, 7 hours, 57 minutes
* Origin: -=> Castle Rock BBS <=- Now Husky HPT Powered! (1337:3/111)