TY - JOUR
T1 - Replacement of the Y450 (c234) phenyl ring in the carboxyl-terminal region of coagulation factor IX causes pleiotropic effects on secretion and enzyme activity
AU - Branchini, Alessio
AU - Campioni, Matteo
AU - Mazzucconi, Maria Gabriella
AU - Biondo, Francesca
AU - Mari, Rosella
AU - Bicocchi, Maria Patrizia
AU - Bernardi, Francesco
AU - Pinotti, Mirko
PY - 2013/10/1
Y1 - 2013/10/1
N2 - The interplay between impaired protein biosynthesis and/or function caused by missense mutations, particularly in relation to specific protein regions, has been poorly investigated. As model we chose the severe p.Y450C mutation in the carboxyl-terminal region of coagulation factor IX (FIX) and, by expression of a panel of recombinant variants, demonstrated the key role of the tyrosine phenyl group for both FIX secretion and coagulant activity. Comparison among highly homologous coagulation serine proteases indicate that additive or compensatory pleiotropic effects on secretion and function by carboxyl-terminal mutations produce life-threatening or mild phenotypes in the presence of similarly reduced protein amounts.
AB - The interplay between impaired protein biosynthesis and/or function caused by missense mutations, particularly in relation to specific protein regions, has been poorly investigated. As model we chose the severe p.Y450C mutation in the carboxyl-terminal region of coagulation factor IX (FIX) and, by expression of a panel of recombinant variants, demonstrated the key role of the tyrosine phenyl group for both FIX secretion and coagulant activity. Comparison among highly homologous coagulation serine proteases indicate that additive or compensatory pleiotropic effects on secretion and function by carboxyl-terminal mutations produce life-threatening or mild phenotypes in the presence of similarly reduced protein amounts.
KW - Carboxyl-terminal region
KW - Coagulation factor IX
KW - Dysfunctional enzyme
KW - Gene expression
KW - Impaired secretion
KW - Missense mutations
UR - http://www.scopus.com/inward/record.url?scp=84884286170&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84884286170&partnerID=8YFLogxK
U2 - 10.1016/j.febslet.2013.08.019
DO - 10.1016/j.febslet.2013.08.019
M3 - Article
C2 - 23994528
AN - SCOPUS:84884286170
VL - 587
SP - 3249
EP - 3253
JO - FEBS Letters
JF - FEBS Letters
SN - 0014-5793
IS - 19
ER -