On the molecular basis of the recognition of angiotensin II (AII) - NMR structure of AII in solution compared with the X-ray structure of AII bound to the mAb Fab131
Φόρτωση...
Ημερομηνία
Συγγραφείς
Tzakos, A. G.
Bonvin, A. M. J. J.
Troganis, A.
Cordopatis, P.
Amzel, M. L.
Gerothanassis, I. P.
van Nuland, N. A. J.
Τίτλος Εφημερίδας
Περιοδικό ISSN
Τίτλος τόμου
Εκδότης
Wiley-Blackwell
Περίληψη
Τύπος
Είδος δημοσίευσης σε συνέδριο
Είδος περιοδικού
peer reviewed
Είδος εκπαιδευτικού υλικού
Όνομα συνεδρίου
Όνομα περιοδικού
European Journal of Biochemistry
Όνομα βιβλίου
Σειρά βιβλίου
Έκδοση βιβλίου
Συμπληρωματικός/δευτερεύων τίτλος
Περιγραφή
The high-resolution 3D structure of the octapeptide hormone angiotensin II (AII) in aqueous solution has been obtained by simulated annealing calculations, using high-resolution NMR-derived restraints. After final refinement in explicit water, a family of 13 structures was obtained with a backbone RMSD of 0.73 +/- 0.23 Angstrom. AII adopts a fairly compact folded structure, with its C-terminus and N-terminus approaching to within approximate to 7.2 Angstrom of each other. The side chains of Arg2, Tyr4, Ile5 and His6 are oriented on one side of a plane defined by the peptide backbone, and the Val3 and Pro7 are pointing in opposite directions. The stabilization of the folded conformation can be explained by the stacking of the Val3 side chain with the Pro7 ring and by a hydrophobic cluster formed by the Tyr4, Ile5 and His6 side chains. Comparison between the NMR-derived structure of AII in aqueous solution and the refined crystal structure of the complex of AII with a high-affinity mAb (Fab131) [Garcia, K.C., Ronco, P.M., Verroust, P.J., Brunger, A.T., Amzel, L.M. (1992) Science 257 , 502-507] provides important quantitative information on two common structural features: (a) a U-shaped structure of the Tyr4-Ile5-His6-Pro7 sequence, which is the most immunogenic epitope of the peptide, with the Asp1 side chain oriented towards the interior of the turn approaching the C-terminus; (b) an Asx-turn-like motif with the side chain aspartate carboxyl group hydrogen-bonded to the main chain NH group of Arg2. It can be concluded that small rearrangements of the epitope 4-7 in the solution structure of AII are required by a mean value of 0.76 +/- 0.03 Angstrom for structure alignment and approximate to 1.27 +/- 0.02 Angstrom for sequence alignment with the X-ray structure of AII bound to the mAb Fab131. These data are interpreted in terms of a biological 'nucleus' conformation of the hormone in solution, which requires a limited number of structural rearrangements for receptor-antigen recognition and binding.
Περιγραφή
Λέξεις-κλειδιά
angiotensin ii, monoclonal antibody, nmr, peptide structure, vib turn, protein-coupled receptors, (aii)-related idiotypic network, chemical-shifts, 3-dimensional structure, monoclonal-antibodies, magnetic-resonance, at(1) receptor, amino-acids, conformation, peptide
Θεματική κατηγορία
Παραπομπή
Σύνδεσμος
<Go to ISI>://000181107400008
http://onlinelibrary.wiley.com/store/10.1046/j.1432-1033.2003.03441.x/asset/j.1432-1033.2003.03441.x.pdf?v=1&t=hmn3ogzj&s=8986ff3ce800ab1d01974705e266d7276cac0e3d
http://onlinelibrary.wiley.com/store/10.1046/j.1432-1033.2003.03441.x/asset/j.1432-1033.2003.03441.x.pdf?v=1&t=hmn3ogzj&s=8986ff3ce800ab1d01974705e266d7276cac0e3d
Γλώσσα
en
Εκδίδον τμήμα/τομέας
Όνομα επιβλέποντος
Εξεταστική επιτροπή
Γενική Περιγραφή / Σχόλια
Ίδρυμα και Σχολή/Τμήμα του υποβάλλοντος
Πανεπιστήμιο Ιωαννίνων. Σχολή Θετικών Επιστημών. Τμήμα Χημείας