Topological analysis of the complex formed between neurokinin A and the NK2 tachykinin receptor
Neurokinin A stimulates physiological responses in the peripheral and central nervous systems upon interacting primarily with the tachykinin NK2 receptor (NK2R). In this study, the structure of NKA bound to the NK2R is characterised by use of fluorescence resonance energy transfer. Four fluorescent...
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Published in | Journal of neurochemistry Vol. 101; no. 2; pp. 506 - 516 |
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Main Authors | , , , , , , |
Format | Journal Article |
Language | English |
Published |
Oxford, UK
Oxford, UK : Blackwell Publishing Ltd
01.04.2007
Blackwell Publishing Ltd Blackwell Wiley |
Subjects | |
Online Access | Get full text |
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Summary: | Neurokinin A stimulates physiological responses in the peripheral and central nervous systems upon interacting primarily with the tachykinin NK2 receptor (NK2R). In this study, the structure of NKA bound to the NK2R is characterised by use of fluorescence resonance energy transfer. Four fluorescent NKA analogues with Texas red introduced at amino acid positions 1, 4, 7 and 10 were prepared. When bound to a NK2R carrying enhanced green fluorescent protein at the N-terminus, all peptides reduce green fluorescent protein fluorescence from 10% to 50% due to energy transfer. The derived donor-acceptor distances are 46, 55, 59 and 69 Å for the fluorophore linked to positions 1-10, respectively. The monotonic increase in distance clearly indicates that the peptide adopts an extended structure when bound to its receptor. The present data are used, in combination with rhodopsin structure, fluorescence studies, photoaffinity labelling and site-directed mutagenesis data to design a computer model of the NKA-NK2R complex. We propose that the N-terminus of NKA is exposed and accessible to the extracellular medium. Subsequent amino acids of the NKA peptide become progressively more buried residues up to approximately one-third of the transmembrane-spanning domain. |
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Bibliography: | http://dx.doi.org/10.1111/j.1471-4159.2007.04473.x The present address of Sannah Zoffmann is the Hoffmann‐La Roche Ltd., PRBD Grenzacher strasse, Bau 70/4, 4070 Basel, Switzerland. The present address of Quoc‐Tuan Do is the Greenpharma 3, allée du titane, 45100 Orléans, France. |
ISSN: | 0022-3042 1471-4159 |
DOI: | 10.1111/j.1471-4159.2007.04473.x |