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J. Biol. Chem., Vol. 276, Issue 4, 2600-2607, January 26, 2001
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From the Department of Cellular and Molecular Physiology,
University of Massachusetts Medical School,
Worcester, Massachusetts 01655 and § Internal Medicine
III, Erasmus University Medical School, 3015GD
Rotterdam, The Netherlands
Type I iodothyronine deiodinase is a ~50-kDa,
integral membrane protein that catalyzes the outer ring deiodination of
thyroxine. Despite the identification and cloning of a 27-kDa
selenoprotein with the catalytic properties of the type I enzyme, the
composition and the physical nature of the active deiodinase are
unknown. In this report, we use a molecular approach to determine
holoenzyme composition, the role of the membrane anchor on enzyme
assembly, and the contribution of individual 27-kDa subunits to
catalysis. Overexpression of an immunologically unique rat 27-kDa
protein in LLC-PK1 cells that contain abundant catalytically active
27-kDa selenoprotein decreased deiodination by ~50%, and >95% of
the LLC-PK1 derived 27-kDa selenoprotein was specifically immune
precipitated by the anti-rat enzyme antibody. The hybrid enzyme had a
molecular mass of 54 kDa and an
s20,w of ~3.5 S indicating that every
native 27-kDa selenoprotein partnered with an inert rat 27-kDa subunit
in a homodimer. Enzyme assembly did not depend on the presence of the
N-terminal membrane anchor of the 27-kDa subunit. Direct visualization
of the deiodinase dimer showed that the holoenzyme was sorted to the
basolateral plasma membrane of the renal epithelial cell.
Characterization of the Subunit Structure of the Catalytically
Active Type I Iodothyronine Deiodinase*
,
*
The costs of publication of this
article were defrayed in part by the
payment of page charges. The article
must therefore be hereby marked
"advertisement" in
accordance with 18 U.S.C. Section
1734 solely to indicate this fact.
To whom correspondence should be addressed: Dept. of Cellular and
Molecular Physiology, 55 Lake Ave. N., Worcester, MA 01655. Tel.:
508-856-6687; Fax: 508-856-4572; E-mail:
jack.leonard@UMASSMED.edu.
Copyright © 2001 by The American Society for Biochemistry and Molecular Biology, Inc.
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