The β104-109 sequence is essential for the secretion of correctly folded single-chain βα horse LH/CG and for its FSH activity

Colette Galet; Florian Guillou; Florence Foulon-Gauze; Yves Combarnous; Maryse Chopineau

doi:10.1677/JOE-09-0141

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The β104-109 sequence is essential for the secretion of correctly folded single-chain βα horse LH/CG and for its FSH activity

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The β104-109 sequence is essential for the secretion of correctly folded single-chain βα horse LH/CG and for its FSH activity

Colette Galet, Florian Guillou, Florence Foulon-Gauze, Yves Combarnous and Maryse Chopineau

Journal of endocrinology, Vol.203(1), pp.167-174

10/01/2009

DOI: 10.1677/JOE-09-0141

PMID: 19589909

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Abstract

The dual LH and FSH activity of the equine LH (eLH)/equine chorionic gonadotropin (eCG) in heterologous species makes eLH/CG a good model to study structure/function relationships of gonadotropins. In order to bypass the problem of intracellular association of the heterodimer, a recombinant single-chain beta alpha eLH/CG was used to identify sequences in the beta-subunit involved in the secretion and activities of the hormone. The C-terminal region of the beta-subunit was progressively truncated. All resulting truncated single-chains were secreted in the media as detected by an anti-beta peptide antibody in reducing conditions. However. using a conformation sensitive ELISA we show that the truncated single-chains were differently recognized: deletion of the last 40 amino acids of the beta-subunit (beta 109 alpha eLH/CG) resulted in a 90% decrease in the recognized correctly folded hormone compared with the full-length beta alpha eLH/CG single-chain and no properly folded hormone was detected in the secretion medium when the last 46 amino acids of the beta-subunit were deleted (beta 103 alpha eLH/CG). We thus focused on the six amino acids sequence 104-109, which belongs to the seat-belt region. Mutation of the 104-109 sequence in alanines in the full-length beta alpha eLH/CG (beta 104-109Ala alpha) led to a 50% decrease in the production of properly folded hormone in COS-7 as well as in alpha T3 pituitary cells. Moreover, the FSH activity of this mutant was decreased by 70% whereas its LH activity remained intact. These data lead us to conclude that the 104-109 region of the beta eLH/CG subunit is essential for the secretion of a fully folded beta alpha eLH/CG and for its FSH activity but not for its LH activity. Journal of Endocrinology (2009) 203, 167-174

Endocrinology & Metabolism

Life Sciences & Biomedicine

Science & Technology

Details

Title: Subtitle: The β104-109 sequence is essential for the secretion of correctly folded single-chain βα horse LH/CG and for its FSH activity
Creators: Colette Galet - Iowa State University
Florian Guillou - Centre National de la Recherche Scientifique
Florence Foulon-Gauze - Physiologie de la Reproduction et des Comportements
Yves Combarnous - Physiologie de la Reproduction et des Comportements
Maryse Chopineau - Physiologie de la Reproduction et des Comportements
Resource Type: Journal article
Publication Details: Journal of endocrinology, Vol.203(1), pp.167-174
DOI: 10.1677/JOE-09-0141
PMID: 19589909
NLM abbreviation: J Endocrinol
ISSN: 0022-0795
eISSN: 1479-6805
Publisher: Bioscientifica Ltd
Number of pages: 8
Grant note: Institut National do la Recherche Agronomique (INRA) Centre National de la Recherche Scientifique (CNRS)
Language: English
Date published: 10/01/2009
Academic Unit: Injury Prevention Research Center; University of Iowa Health Care
Record Identifier: 9985137927502771

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