An unusual protein structure called a
"corrugated beta sheet", first predicted in 1953, has now been
created in the laboratory and characterized in detail using X-ray
crystallography.

The new findings, published in Chemical
Science in July, may enable the rational design of unique materials based
on corrugated sheet-like structures.

Jevgenij Raskatov, associate professor of
chemistry and biochemistry at the University of California, Santa Cruz and
corresponding author of the paper, said: "Our study establishes the
corrugated beta sheet configuration as a motif with universal characteristics,
and opens the way for structure-based design of unique molecular structures
with the potential for material development and biomedical applications."

Proteins come in ever-changing shapes and
sizes and play a wide variety of structural and functional roles in living
cells. Certain common structural motifs, such as alpha helices, are found in
many protein structures.

Corrugated sheet is a variation of β sheet,
which is a famous structural motif found in thousands of proteins. Linus
Pauling and Robert Corey described corrugated beta flakes in 1953, and two
years ago they proposed the concept of corrugated beta flakes. Although the
folded beta sheet is well-known and often simply called beta sheet, corrugated
beta sheets have remained largely a theoretical structure for decades.

In a study previously published in 2021,
Raskatov's team reported that by mixing small peptides with an equal amount of
mirror images, they obtained corrugated beta sheet structures. The researchers
used the mirror-image form of triphenylalanine, a short peptide composed of
three phenylalanine amino acids. The mirror-image polypeptides bind in pairs to
form "dimers" with the predicted structure, but they do not form the
extended, periodically corrugated beta-sheet topography assumed by Pauling and
Corey.

"The dimers clustered together to form
a chevron-shaped layer structure, which raised doubts about whether a
periodically corrugated beta-sheet structure was feasible," Raskatov said.

In the new study, the researchers replaced
one of the triphenylalanines with other amino acids, resulting in a slightly
different tripeptide and its mirror image. Using these new tripeptides, they
were able to create three different polymeric peptide systems that form
extended layers of antiparallel corrugated beta sheets in which mirror-image
peptide chains are arranged in an alternating fashion. The X-ray
crystallography results showed that the crystal structure was basically
consistent with Pauling and Corey's predictions.

One of the paper's first authors is Raskatov's
lab staff Amaruka Hazari and UCLA's Michael Sawaya. Other co-authors include
Timothy Johnstone of UC Santa Cruz and Niko Vlahakis, David Boyer, Jose
Rodriguez and David Eisenberg of UCLA. This research was supported by the
National Institutes of Health.