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Replacement of the Y450 (c234) phenyl ring in the carboxyl‐terminal region of coagulation factor IX causes pleiotropic effects on secretion and enzyme activity
Author(s) -
Branchini Alessio,
Campioni Matteo,
Mazzucconi Maria Gabriella,
Biondo Francesca,
Mari Rosella,
Bicocchi Maria Patrizia,
Bernardi Francesco,
Pinotti Mirko
Publication year - 2013
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/j.febslet.2013.08.019
Subject(s) - secretion , coagulation , enzyme , chemistry , ring (chemistry) , terminal (telecommunication) , biochemistry , stereochemistry , medicine , organic chemistry , telecommunications , computer science
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.