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 a-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. (C) 2010 Elsevier Inc. All rights reserved.