title: The NMR solution structure of the ubiquitin homology domain of Bcl-2-associated athanogene 1 (BAG-1-UBH) from Mus musculus.
abstract: 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-1-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.
authors.affiliation: Department of Chemistry, National Tsing Hua University, Hsinchu 30013, Taiwan, ROC. d9623541@oz.nthu.edu.tw
authors.forename: Hsiao-Wen
authors.initials: HW
authors.lastname: Huang
authors.forename: C
authors.initials: C
authors.lastname: Yu
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D004268:DNA-Binding Proteins / Q000737:chemistry*; D066257:Heparin-binding EGF-like Growth Factor; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000737:chemistry; D051379:Mice; D008969:Molecular Sequence Data; D019906:Nuclear Magnetic Resonance, Biomolecular; D025941:Protein Interaction Mapping; D017434:Protein Structure, Tertiary; D012996:Solutions; D014157:Transcription Factors / Q000737:chemistry*; D025801:Ubiquitin / Q000737:chemistry*
chemical_list: C091732:BCL2-associated athanogene 1 protein; D004268:DNA-Binding Proteins; C587883:HBEGF protein, human; C587884:Hbegf protein, mouse; D066257:Heparin-binding EGF-like Growth Factor; D036341:Intercellular Signaling Peptides and Proteins; D012996:Solutions; D014157:Transcription Factors; D025801:Ubiquitin