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

J. Biol. Chem., Vol. 279, Issue 43, 44286-44293, October 22, 2004

This Article Full Text Full Text (PDF) All Versions of this Article: 279/43/44286    most recent M408386200v1 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 Garcia-Campayo, V. Articles by Boime, I. Search for Related Content PubMed PubMed Citation Articles by Garcia-Campayo, V. Articles by Boime, I. Social Bookmarking                      What's this?

A Single-chain Bifunctional Gonadotropin Analog Is Secreted from Chinese Hamster Ovary Cells as Two Distinct Bioactive Species^*

Vicenta Garcia-Campayo, Albina Jablonka-Shariff, and Irving Boime

From the Department of Molecular Biology & Pharmacology, Washington University School of Medicine, St. Louis, Missouri 63110

One of the major developments in exploring structure activity relationships of the glycoprotein hormone family was the genetic engineering of single chains comprised of the common subunit and one or more of the hormone-specific subunits tandemly arranged. These studies indicate that there is a structural permissiveness in the quaternary relationships between the subunits and biological activity. However, the conformational relationships between the ligand and the receptor are unclear. Bifunctional triple-domain analogs represent an ideal model to address this issue. Does a single molecule possess the ability to simultaneously interact with both specific receptors or are there two functionally distinct species in the chimeric population? Here we show, using a preadsorption protocol comprised of Chinese hamster ovary cells expressing either the luteinizing hormone (LH)/chorionic gonadotropin (CG) or follicle-stimulating hormone (FSH) receptor, that at least two distinct bioactive populations of the dually active triple-domain chimera FSH-CG- are synthesized, each corresponding to a single activity (CG or FSH). Furthermore, we show that these bioactive populations form distinct stable heterodimer-like contacts. That there is not a single biologically active species formed during synthesis of the chimera implies that in vivo the heterodimer exists in multiple conformations and is not a static rigid molecule.

Received for publication, July 23, 2004 , and in revised form, August 9, 2004.

^* 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.

To whom correspondence should be addressed: Dept. of Molecular Biology & Pharmacology, Washington University School of Medicine, 660 S. Euclid, Box 8103, St. Louis, MO 63110. Tel.: 314-362-2556; Fax: 314-361-3560; E-mail: IBoime{at}molecool.wustl.edu.

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

This article has been cited by other articles:

				A. Jablonka-Shariff, C. A. Pearl, A. Comstock, and I. Boime A Carboxyl-terminal Sequence in the Lutropin {beta} Subunit Contributes to the Sorting of Lutropin to the Regulated Pathway J. Biol. Chem., April 25, 2008; 283(17): 11485 - 11492. [Abstract] [Full Text] [PDF]

				P. Nurwakagari, A. Breit, C. Hess, H. Salman-Livny, D. Ben-Menahem, and T. Gudermann A conformational contribution of the luteinizing hormone-receptor ectodomain to receptor activation J. Mol. Endocrinol., February 1, 2007; 38(2): 259 - 275. [Abstract] [Full Text] [PDF]

				G. Han, K. Gable, L. Yan, M. J. Allen, W. H. Wilson, P. Moitra, J. M. Harmon, and T. M. Dunn Expression of a Novel Marine Viral Single-chain Serine Palmitoyltransferase and Construction of Yeast and Mammalian Single-chain Chimera J. Biol. Chem., December 29, 2006; 281(52): 39935 - 39942. [Abstract] [Full Text] [PDF]

				A. Jablonka-Shariff, T. R. Kumar, J. Eklund, A. Comstock, and I. Boime Single-Chain, Triple-Domain Gonadotropin Analogs with Disulfide Bond Mutations in the {alpha}-Subunit Elicit Dual Follitropin and Lutropin Activities in Vivo Mol. Endocrinol., June 1, 2006; 20(6): 1437 - 1446. [Abstract] [Full Text] [PDF]