Dedicated to the memory of Prof. Rafael Suau.
Article first published online: 9 AUG 2011
Copyright © 2011 Wiley Periodicals, Inc.
Volume 97, Issue 1, pages 45–53, January 2012
How to Cite
Pérez-Castells, J., Martín-Santamaría, S., Nieto, L., Ramos, A., Martínez, A., Pascual-Teresa, B. d. and Jiménez-Barbero, J. (2012), Structure of micelle-bound adrenomedullin: A first step toward the analysis of its interactions with receptors and small molecules. Biopolymers, 97: 45–53. doi: 10.1002/bip.21700
This article was originally published online as an accepted preprint. The “Published Online” date corresponds to the preprint version. You can request a copy of the preprint by emailing the Biopolymers editorial office at biopolymers@wiley. com
- Issue published online: 24 OCT 2011
- Article first published online: 9 AUG 2011
- Manuscript Accepted: 11 JUL 2011
- Manuscript Revised: 10 JUL 2011
- Manuscript Received: 26 MAY 2011
- MICINN Spanish Ministry of Science and Innovation. Grant Numbers: SAF2005-02608, SAF2008-00945, SAF2009-13240-C02-01, CTQ2009-08536
- membrane-like environment;
Adrenomedullin (AM) is a regulatory peptide which plays many physiological roles including vasodilatation, bronchodilatation, hormone secretion regulation, growth, apoptosis, angiogenesis, and antimicrobial activities, among others. These regulatory activities make AM a relevant player in the pathophysiology of important diseases such as cardiovascular and renal conditions, cancer, and diabetes. Therefore, molecules that target the AM system have been proposed as having therapeutic potential. To guide the design and characterization of such molecules, we elucidated the three-dimensional structure of AM in a membrane mimicking medium using NMR spectroscopy methods. Under the employed experimental conditions, the structure can be described as composed by a central α-helical region, spanning about one third of its total length, flanked by two disordered segments at both N- and C-termini. The structure of AM in water is completely disordered. The 22–34 region of AM has a general tendency to adopt a helical structure under the employed experimental conditions. Furthermore, the study of the interaction of AM with two of its modulators has also been performed by using chemical shift perturbation analysis NMR methods with two-dimensional (2D)-TOCSY experiments, assisted with molecular modeling protocols. We expect these results will help in better understanding the interactions of AM with its receptor and binding proteins/molecules and in the development of novel modulators of AM activities. © 2011 Wiley Periodicals, Inc. Biopolymers 97: 45–53, 2012.