| Title | Structural and functional characterization of the dimerization sites of Soluble Guanylyl Cyclase | |
| Author | Z. Zhou1, Ch. Roussos1 and A. Papapetropoulos1,2
1George P. Livanos-Marianthi Simou Laboratories, Department of Critical Care and Pulmonary Services, Evangelismos Hospital, University of Athens School of Medicine and 2Department of Molecular Pharmacology, School of Pharmacy, University of Patras, Patra, Greece |
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| Citation | Zhou, Z., Roussos, C. and Papapetropoulos, A.: Structural and functional characterization of the dimerization sites of Soluble Guanylyl Cyclase, Epitheorese Klin. Farmakol. Farmakokinet. 18(1): 36-38 (2004) | |
| Publication Date | Accepted for publication: 2004 | |
| Full Text Language | English | |
| Order – Buy | Ηλεκτρονική Μορφή: pdf (10 €) – Digital Type: pdf (10 €) pharmakonpress[at]pharmakonpress[.]gr | |
| Keywords | sGC, Soluble Quanylyl Cyclase | |
| Other Terms | review article | |
| Summary | Soluble guanylyl cyclase (sGC) is a ubiquitous enzyme that functions as a receptor for nitric oxide. In spite of the obligate heterodimeric nature of sGC, the sequence mediating subunit association have remained elusive. Our initial screening for the interaction site(s) demonstrated that two regions of each subunit, i.e. the regulatory domain and the central region, are involved in heterodimer formation of the most common sGC isoenzyme, α1/ β1. To precisely map the relevant segments in the βι subunit, we constructed multiple N- and C-terminal deletion variants and co-transfected them with full-length α1 in COS cells. Immunoprécipitation revealed that a sequence segment spanning positions 204 to 408 mediates binding of α1 to β1. Fusion of the α1 dimerization region to EGFP conferred binding activity to the recipient protein. Analysis of deletion constructs lacking portions of the dimerization region identified two distinct sites in βι that contribute importantly to its interaction with α1 i.e. an N- terminal binding site (NBS) covering positions 204 to 244 and a C-terminal binding site at 379 to 408 (CBS). Both NBS and CBS are crucial for sGC function as deletion of either site rendered sGC inactive. We conclude that the dimerization region of β1 extends over 205 residues of its regulatory and central domains, and that two discontinuous sites of 41 and 30 residues, respectively facilitate binding of β1 to the α1 subunit of sGC. | |
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Online ISSN 1011-6575
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| ΕΤΗΣΙΑ ΣΥΝΔΡΟΜΗ 2004 – ANNUAL SUBSCRIPTION 2004 | |
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