BAG-1 (Bcl-2-associated athanogene 1), a multifunctional anti-apoptotic protein known to interact with various cellular proteins, was isolated using its interaction with the anti-apoptotic protein, Bcl-2. A 97-amino acid segment that includes the ubiquitin homology (UBH) domain of mouse BAG-1 (mBAG-1) interacts with a peptide corresponding to the cytoplasmic tail (CT) domain of proHB-EGF. This protein-peptide interaction is likely to have functional significance, as the two species exhibit a synergistic cytoprotective effect. In this study, we determined the solution structure of mBAG-T-UBH and investigated its interaction with the proHB-EGF-CT peptide using isothermal titration calorimetry and NMR spectroscopy. The solution structure of mBAG-1-UBH was shown to be similar to the previously reported structure of hBAG-1-UBH (PDB code 1WXV). However, their electrostatic potential maps demonstrated some differences in the UBH motifs that may be important for protein-peptide interaction. An NMR titration experiment demonstrated that residues 23-26 and residues 89-94 of mBAG-1-UBH are important for its molecular interaction with the peptide proHB-EGF-CT. BAG-1-UBH shares some biological functions with ubiquitin including the formation of polyubiquitin chain and the proteasomal protein degradation. The unique cytoprotective activity suggests mBAG-1-UBH to be an interesting ubiquitin-like protein with distinct biological functions. Here, we first reported the solution structure of mBAG-1-UBH and the growth factor precursor-interacting motif on the protein. For detail understanding about the binding interface and the mechanism of interaction, the study on mBAG-1-UBH/proHB-EGF-CT complex structure is necessary. (C) 2013 Elsevier Inc. All rights reserved.