HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

J. Biol. Chem., Vol. 280, Issue 46, 38395-38402, November 18, 2005

This Article Full Text Full Text (PDF) All Versions of this Article: 280/46/38395    most recent M505983200v1 Submit a Letter to Editor Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Maiorino, M. Articles by Ursini, F. Search for Related Content PubMed PubMed Citation Articles by Maiorino, M. Articles by Ursini, F. Social Bookmarking                      What's this?

Functional Interaction of Phospholipid Hydroperoxide Glutathione Peroxidase with Sperm Mitochondrion-associated Cysteine-rich Protein Discloses the Adjacent Cysteine Motif as a New Substrate of the Selenoperoxidase^*

Matilde Maiorino, Antonella Roveri, Louise Benazzi, Valentina Bosello, Pierluigi Mauri, Stefano Toppo, Silvio C. E. Tosatto¶1, and Fulvio Ursini2

From the Department of Biological Chemistry and ^¶Department of Biology and CRIBI Biotechnology Centre, Viale G. Colombo 3, University of Padova, I-35121 Padova and the Institute for Biomedical Technologies, National Research Council, Viale Fratelli Cervi 93, I-2090 Segrate (Milano), Italy

The mitochondrial capsule is a selenium- and disulfide-rich structure enchasing the outer mitochondrial membrane of mammalian spermatozoa. Among the proteins solubilized from the sperm mitochondrial capsule, we confirmed, by using a proteomic approach, the presence of phospholipid hydroperoxide glutathione peroxidase (PHGPx) as a major component, and we also identified the sperm mitochondrion-associated cysteine-rich protein (SMCP) and fragments/aggregates of specific keratins that previously escaped detection (Ursini, F., Heim, S., Kiess, M., Maiorino, M., Roveri, A., Wissing, J., and Flohé, L. (1999) Science 285, 1393-1396). The evidence for a functional association between PHGPx, SMCP, and keratins is further supported by the identification of a sequence motif of regularly spaced Cys-Cys doublets common to SMCP and high sulfur keratin-associated proteins, involved in bundling hair shaft keratin by disulfide cross-linking. Following the oxidative polymerization of mitochondrial capsule proteins, catalyzed by PHGPx, two-dimensional redox electrophoresis analysis showed homo- and heteropolymers of SMCP and PHGPx, together with other minor components. Adjacent cysteine residues in SMCP peptides are oxidized to cystine by PHGPx. This unusual disulfide is known to drive, by reshuffling oxidative protein folding. On this basis we propose that oxidative polymerization of the mitochondrial capsule is primed by the formation of cystine on SMCP, followed by reshuffling. Occurrence of reshuffling is further supported by the calculated thermodynamic gain of the process. This study suggests a new mechanism where selenium catalysis drives the cross-linking of structural elements of the cytoskeleton via the oxidation of a keratin-associated protein.

Received for publication, June 1, 2005 , and in revised form, July 29, 2005.

^* This work was supported by the Italian Ministry of University and Scientific Research Grants PRIN 2003038920_002 (to M. M.) and 2004054995_001 (to F. U.). The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

¹ Funded by a "Rientro dei cervelli" grant from the Italian Ministry of Education, and Research (MIUR).

² To whom correspondence should be addressed: Dept. of Biological Chemistry, Viale G. Colombo, 3, I-35121 Padova, Italy. Tel.: 39-049-8276104; Fax: 39-049-8073310; E-mail: fulvio.ursini{at}unipd.it.

CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

This article has been cited by other articles:

				F. Briani, S. Curti, F. Rossi, T. Carzaniga, P. Mauri, and G. Deho Polynucleotide phosphorylase hinders mRNA degradation upon ribosomal protein S1 overexpression in Escherichia coli RNA, November 1, 2008; 14(11): 2417 - 2429. [Abstract] [Full Text] [PDF]