CHARACTERIZATION OF 2 NOVEL LY-6 GENES - PROTEIN-SEQUENCE AND POTENTIAL STRUCTURAL SIMILARITY TO ALPHA-BUNGAROTOXIN AND OTHER NEUROTOXINS

Genomic clones cross-hybridizing with Ly-6A.2 cDNA were isolated and c haracterized for functional Ly-6-related genes. Two new Ly-6 genes, de signated Ly-6F.1 and Ly-6G.1, were found to have high nucleotide homol ogy (greater-than-or-equal-to 70%) and the characteristic four exon ge ne organization of Ly-6A/E and Ly-6C. By a PCR-based assay, Ly-6G.1 mR NA was readily found in bone marrow, whereas Ly-6F.1 mRNA was not dete cted in lymphoid tissues. Thus, Ly-6G.1 represents an additional Ly-6 gene with apparent selective expression in hematopoietic cells distinc t from Ly-6A/E and Ly-6C. Using the available deduced protein sequence data for mature Ly-6 proteins, searches of the database uncovered an evolutionary relationship of Ly-6 proteins with neurotoxins isolated f rom snake venoms. The protein sequence conservation between the two gr oups was selective for, but not limited to, residues in neurotoxins th at have been found to be important for their tertiary structures. From this relationship, we propose a neurotoxin-like structure for Ly-6- a nd Ly-6-related proteins, such as CD59.