Transferred Cross-Correlated Relaxation Complements Transferred NOE:  Structure of an IL-4R-Derived Peptide Bound to STAT-6

A new NMR method is proposed which enables the measurement of projection angles in the bound conformation of a weakly binding ligand complexed to its receptor. The method is based on the cross-correlated relaxation mechanism. In analogy to the transferred NOE experiment (trNOE), cross-correlated rel...

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Bibliographic Details
Published in:Journal of the American Chemical Society 1999-03, Vol.121 (9), p.1949-1953
Main Authors: Blommers, Marcel J. J, Stark, Wilhelm, Jones, Carol E, Head, Denis, Owen, Charles E, Jahnke, Wolfgang
Format: Article
Language:English
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Summary:A new NMR method is proposed which enables the measurement of projection angles in the bound conformation of a weakly binding ligand complexed to its receptor. The method is based on the cross-correlated relaxation mechanism. In analogy to the transferred NOE experiment (trNOE), cross-correlated relaxation can be transferred and measured at the resonances of the free ligand (trCCR), provided the k off rate is within the time scale of the experiment. The concept is validated by the structure determination of an interleukin-4 (IL-4) receptor-derived partially 13C- and 15N-labeled phosphotyrosine peptide ligated to STAT-6. Distances have been obtained by trNOE experiments, and the torsion angle Pro(ψ) has been determined using trCCR, measuring either cross-correlated HN−N/Hα−Cα dipole−dipole relaxation or cross-correlated Hα−Cα dipole/CO chemical shift anisotropy relaxation. The resulting structure has been described.
ISSN:0002-7863
1520-5126
DOI:10.1021/ja9836545