Yeast impact homology 1 (Yih1) is part of a conserved eukaryotic ribosomal stress response to amino-acid starvation, interacting with kinase GCN2. We report the structures of the two domains of Yih1, determined by multidimensional NMR methods on full-length protein. However, NMR methods initially failed to establish what interaction, if any, occurred between the two domains. SAXS data, protein cross-linking combined with tryptic/chymotryptic digestion and tandem mass-spectrometry, paramagnetic solvent relaxation measurements, NMR chemical shifts of selected mutants and careful analysis of NOE data established a flexible but compact structure in which a key residue of interaction with GCN1, Glu106, is buried. The structural results suggest a mechanism of action of Yih1.