Biological characterization and structure based prediction of insulin-like growth factor binding protein-5.

The insulin-like growth factor binding protein (IGFBP) family has been shown to play a role in various functions such as cell growth, cell death, cell motility, and tissue remodeling. Among the 7 IGFBP family members, IGFBP-5 was recently shown to play an important role in breast cancer biology, especially in breast cancer metastasis. The three-dimensional structure of the mini IGFBP-5 domain (amino acids 40-92) is known, but structural information on the complete N, L, and C domains remains unknown. Due to difficulties associated with expression and crystallization of full-length IGFBP-5, fragments have more frequently been studied. In this study, IGFBP-5 structures containing N, L, and C domains were separately modeled from solved structures in protein data bank (PDB). In addition, the L domain of IGFBP-5 was expressed in Escherichia coli and purified for studying its structural characterization. Despite very low sequence homology, the novel L domain structure of IGFBP-5 was unexpectedly similar to that of the corepressor of repressor element-1 silencing transcription factor (CoREST) linker in the lysine-specific demethylase 1 (LSD1)-CoREST complex. The purified L domain existed as a homogenous dimer in glutaraldehyde cross-linking and exhibited a typical α-helix structure in the circular dichroism (CD) assay. This study has potential applications in medicine and other fields such as drug design, mutational study, and disease prediction.