Origene_Jan2021_ProperAntibodyDesignKeeps - 15

Proper Antibody Design Keeps Specificity In Mind

Nanobody Approach
Prevents the Culling of Imperfect
but Still-Functional Proteins

T

o ensure the health of the cell's protein
herds, the ubiquitination system marks
misfolded or damaged proteins for

destruction. But the ubiquitination system can
be overzealous, targeting proteins that are less
than perfect, but still able to carry out their usual,
useful functions. Conceivably, if less-than-perfect
proteins were to be spared, they could serve therapeutic purposes.
This possibility is being explored by scientists
based at Columbia University. They are developing
engineered deubiquitinases (enDUBs) that can
Selvanegra / Getty Images

reverse the ubiquitination system's ruthless machinations. Importantly, the enDUBs can discriminate
between proteins that should be spared, and those
that really do need to be destroyed.
Details of this work recently appeared in Nature
Methods, in an article titled, " Targeted deubiquitination rescues distinct trafficking-deficient

Proteasomes are a large molecular machine that degrade
unneeded or damaged proteins that have been tagged
with polyubiquitin (yellow). The ubiquitin hydrolase
(violet) detaches ubiquitin from the protein that is then
unfolded and degraded into small peptides (bottom).

ion channelopathies. " This article describes how
the Columbia scientists' approach, which relies

ubiquitin chain removal from target proteins to

on a new technology that incorporates synthetic

rescue the functional expression of disparate

llama antibodies, could be used to treat dozens of

mutant ion channels that underlie long QT

diseases, including cystic fibrosis, that arise from

syndrome (LQT) and cystic fibrosis (CF), " the

the destruction of imperfect but still perfectly

article's authors wrote. " In an LQT type 1 (LQT1)

functional proteins.

cardiomyocyte model, enDUB treatment

" We developed enDUBs that enable selective

restored delayed rectifier potassium currents and
GENengnews.com

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https://www.nature.com/articles/s41592-020-00992-6 https://www.nature.com/articles/s41592-020-00992-6 https://www.nature.com/articles/s41592-020-00992-6 http://www.GENengnews.com

Origene_Jan2021_ProperAntibodyDesignKeeps

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Origene_Jan2021_ProperAntibodyDesignKeeps - Contents
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