COMPARISON OF CLARA CELL PHOSPHOLIPID-BINDING PROTEIN STRUCTURES. T.C. Umland¹, S. Swaminathan^1,2, W. Furey^1,2 and M. Sax^1,2. ¹VA Medical Center, PO Box 12055, University Dr. C, Pittsburgh, PA 15240 and ²University of Pittsburgh, Pittsburgh, PA 15260

Crystal structures of Clara cell phospholipid-binding protein (CCPBP) have been determine for protein isolated from both human and rat. In the case of the human protein, the three-dimensional structure is known for two different crystal forms. Thus, structural comparisons between the same protein in different crystallographic environments, as well as comparisons between CCPBP from different species is possible. CCPBP is secreted by Clara cells into the distal airways of the lung. It has also been identified in other tissue and is the counterpart to the protein uteroglobin from rabbit and related species. The protein is a homodimer weighing approximately 16 kDa. It is covalently bound together in an anti-parallel manner by two disulfide bonds, and a large interior cavity is formed between the two monomers. The dimer may remain intact after reduction of the disulfide bonds, and the presence or absence of these bonds control access to the interior cavity, in which ligand binding occurs. CCPBP may bind phosphatidylinositol, phosphatidylcholine, several PCB derivatives, and progesterone within this cavity. The comparison of the several known structures of CCPBP will provide insight into the mechanism of ligand binding and the differences in ligand affinity by the protein from various species.