TY - JOUR
T1 - Human Viperin Causes Radical SAM-Dependent Elongation of Escherichia coli, Hinting at Its Physiological Role
AU - Nelp, Micah T.
AU - Young, Anthony P.
AU - Stepanski, Branden M.
AU - Bandarian, Vahe
N1 - Publisher Copyright:
© 2017 American Chemical Society.
PY - 2017/8/1
Y1 - 2017/8/1
N2 - Viperin (virus inhibitory protein, endoplasmic reticulum-associated, interferon-inducible) is a widely distributed protein that is expressed in response to infection and causes antiviral effects against a broad spectrum of viruses. Viperin is a member of the radical S-adenosyl-l-methionine (SAM) superfamily of enzymes, which typically employ a 4Fe-4S cluster to reductively cleave SAM to initiate chemistry. Though the specific reaction catalyzed by viperin remains unknown, it has been shown that expression of viperin causes an increase in the fluidity of lipid membranes, which impedes the budding of nascent viral particles from the membrane inhibiting propagation of the infection. Herein, we show that expression of the human viperin homologue induces a dramatically elongated morphology of the host Escherichia coli cells. Mutation of an essential cysteine that coordinates the radical SAM cluster abrogates this effect. Thus, the native radical SAM activity of viperin is likely occurring in the host bacteria, indicating the elusive substrate is shared between both bacteria and humans, significantly narrowing the range of potential candidate substrates and providing a convenient bacterial platform from which future studies can occur.
AB - Viperin (virus inhibitory protein, endoplasmic reticulum-associated, interferon-inducible) is a widely distributed protein that is expressed in response to infection and causes antiviral effects against a broad spectrum of viruses. Viperin is a member of the radical S-adenosyl-l-methionine (SAM) superfamily of enzymes, which typically employ a 4Fe-4S cluster to reductively cleave SAM to initiate chemistry. Though the specific reaction catalyzed by viperin remains unknown, it has been shown that expression of viperin causes an increase in the fluidity of lipid membranes, which impedes the budding of nascent viral particles from the membrane inhibiting propagation of the infection. Herein, we show that expression of the human viperin homologue induces a dramatically elongated morphology of the host Escherichia coli cells. Mutation of an essential cysteine that coordinates the radical SAM cluster abrogates this effect. Thus, the native radical SAM activity of viperin is likely occurring in the host bacteria, indicating the elusive substrate is shared between both bacteria and humans, significantly narrowing the range of potential candidate substrates and providing a convenient bacterial platform from which future studies can occur.
UR - http://www.scopus.com/inward/record.url?scp=85026755942&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85026755942&partnerID=8YFLogxK
U2 - 10.1021/acs.biochem.7b00608
DO - 10.1021/acs.biochem.7b00608
M3 - Article
C2 - 28708394
AN - SCOPUS:85026755942
SN - 0006-2960
VL - 56
SP - 3874
EP - 3876
JO - Biochemistry
JF - Biochemistry
IS - 30
ER -