154 10 JULY 2020 • VOL 369 ISSUE 6500
STRUCTURAL BIOLOGY
Engineering a toxin
Developing drugs that target a
specific subtype in a G protein–
coupled receptor (GPCR) family
is a major challenge. Maeda et al.
examined the basis of specificity
of a snake venom toxin binding to
muscarinic acetylcholine recep-
tors (MAChRs), which mediate
many functions of the central
and parasympathetic nervous
systems. They determined a
structure that shows why the
mamba venom toxin MT7 is spe-
cific for one receptor, M 1 AChR,
and also explains how it inhibits
downstream signaling. Based on
this structure, they engineered
MT7 to be selective for another
receptor, M 2 AChR, instead of
M 1 ChR. The toxin may present a
promising scaffold for developing
specific GPCR modulators. —VV
Science, this issue p. 161
BIOCHEMISTRY
Conserved redox
regulation of kinases
The effects of pathological
oxidative stress are partially
mediated through functional
modification of various proteins.
A pair of papers show that the
oxidation of kinases at evolu-
tionarily conserved cysteine
residues regulates cell metabo-
lism and mitosis. Shrestha et
al. found that oxidation of the
diabetes-associated metabolic
kinase FN3K promoted its
functional oligomerization and
altered cellular redox status.
Byrne et al. found that oxida-
tion of mitotic kinases in human
cells and yeast suppressed
kinase catalytic activity and
impaired cellular division in
yeast. —LKF
Sci. Transl. Med. 12 , eaaz6313,
eaax2713 (2020).Lingual (from inside out) tooth
addition, observed in modern fishes
such as this great white shark,
has now also been observed in fossils
of basal jawed vertebrates.RESEARCHIN SCIENCE JOURNALS
Edited by Michael Funk
PALEONTOLOGYTeeth and jaws
T
he first vertebrates were
jawless, much like a modern
hagfish. There has been
a lot of interest in how
these forms transitioned
to having jaws like most of their
descendants, including humans.
Much of our understanding of
this process has focused on how
the teeth are replaced relative
to the jaw. Previous theories
suggested that tooth growth
that occurred lingually—or
from inside out as in modern
fishes—was a derived condition.
Vaškaninová et al. vertebrates,
suggesting that it may have been
ancestral. —SNV
Science, this issue p. 211Liver cells grown in a
custom bioreactor, as seen
in an artist’s conception, can provide
some support in a model of acute liver failure.BIOENGINEERING
Beneficial
bioartificial livers
Bioartificial livers are an
attractive option as a bridge to
transplant or to promote liver
regeneration in cases of acute
liver failure. Li et al. tested an
extracorporeal bioartificial liver
system composed of human
liver progenitor-like cells cul-
tured on macroporous scaffoldsin a bioreactor that provides
alternating air-liquid exposure.
Three hours of treatment
improved survival, reducing
inflammation and promoting
native liver regeneration in pigs
with drug-induced acute liver
failure. These results suggest
that extracorporeal, cell-based
bioartificial livers may be a prom-
ising treatment for acute liver
failure. —CC
Sci. Transl. Med. 12 , eaba5146 (2020).CREDITS: (PHOTO) DAVID FLEETHAM/ALAMY STOCK PHOTO; (ILLUSTRATION) SHANGHAI CELLIVER BIOTECHNOLOGY CO. LTD.sciencemag.org SCIENCEjixiansheng