Prp2Op is the homolog of mammalian RCC1 (regulator of chromosome condensation 1) in Saccharomyces cerevisiae, which acts as the guanine nucleotide exchange factor (GEF) for Gsp1p (yeast Ran). Prp2Op plays multiple roles in mRNA metabolism, nucleocytoplasmic transport and mitosis regulation. Prp2Op also functions as a linker between chromatin and nuclear pore complex (NPC) which regulates the NPC-mediated boundary activity (BA). Prp2Op contains an N-terminal nuclear localization signal (NLS) and a typical RCC1-like domain (RLD). Here we present the 1.9 angstrom crystal structure of the RCC1-like domain of Prp20p, which exhibits a classical seven-bladed beta-propeller. We also proved that the additional beta-wedge in Prp2Op is essential for the interaction between Prp2Op and Gsp1p. Based on this structure, we built a complex model of Prp2Op and Gsp1 p which was optimized by molecular dynamics (MD) simulations. Our model reveals that Prp2Op and RCC1 share similar Ran GTPase binding mode. In addition, we also studied the histone-binding property of Prp2Op in vitro. (C) 2010 Elsevier Inc. All rights reserved.