[Frontiers in Bioscience E4, 1150-1156, January 1, 2012] 1150 Towards three-dimensional structural analysis of (pro)renin receptor Akio Ebihara 1 , Tsutomu Nakagawa 1 , Chiaki Nakane 2 , Nurun A.H.M. Nabi 1 , Fumiaki Suzuki 1,2 1 Faculty of Applied Biological Sciences, Gifu University, 1-1 Yanagido, Gifu, 501-1193, Japan, 2 Graduate School of Applied Biological Sciences, Gifu University, 1-1 Yanagido, Gifu, 501-1193, Japan TABLE OF CONTENTS 1. Abstract 2. Introduction 3. Amino acid sequence 4. Receptor binding 5. Structure prediction 6. Towards three-dimensional structural analysis 7. Conclusion 8. Acknowledgements 9. References 1. ABSTRACT The (pro)renin receptor is a single-spanning membrane protein that binds both renin and its inactive precursor prorenin. The receptor binding enhances the catalytic activity of renin and induces non-proteolytic activation of prorenin as well as triggers intracellular signaling with either renin or prorenin as a ligand. Three- dimensional structural information of (pro)renin receptor is important to understand the receptor binding. This information is not available due to the lack of its three- dimensional structure. In this review, we summarize the binding properties of (pro)renin receptor, provide the results of structure prediction and point out the issues to be tackled towards three-dimensional structural analysis of this receptor. 2. INTRODUCTION The renin-angiotensin system plays an important role in the regulation of blood pressure and electrolyte balance (1). A key enzyme of this system, renin (EC 3.4.23.15), specifically cleaves its macromolecular substrate, angiotensinogen, to release the N-terminal decapeptide, angiotensin I. This enzymatic reaction is the first step to produce the potent vasoconstricting octapeptide, angiotensin II. Prorenin is the inactive precursor of renin (2, 3). It has a prosegment of 43 amino acid residues attached to the N-terminus of mature renin consisting of 340 amino acid residues. The prosegment masks the active site of renin, thereby preventing the access of angiotensinogen. Prorenin does not self-activate. The blood circulating level of prorenin is 10 times higher than