The knowledge of the distribution of ligand binding sites on extracellular domains of cell-surface molecules is important both in basic research and in the context of drug development. Mapping of binding sites of pathogens on the cell-surface molecules that they use for entry into the cell may be a first step toward the design of therapeutics. For example, the binding site of HIV on T-cells has been mapped to the first immunoglobulin-like domain of the CD4 molecule (1 – 6 ), the binding site of Plasmodium falciparum -infected erythrocytes on venular endothelium resides in the first immunoglobulin-like domain of ICAM-1 (7 ,8 ), and the binding site of rhinovirus has been localized in the same domain of this molecule (9 –11 ). Many of the interactions that have been characterized at the submolecular level in recent years have been studied by analyzing the binding behavior of truncated molecules expressed either in bacteria or by eukaryotic cell transfection.