Gonorrhea remains one of the most common infectious diseases and eludes control by means other than vaccination. For a meaningful immunoprophylactic program, information on the structure-function relationship of the surface antigens with host components are needed. The proposed work consists of determining the primary structure of proteins I, proteins II, and pili by standard DNA and protein sequencing techniques. Currently available cloned genes will be used and additional ones will be isolated by hybridization selection with the cloned genes already available, with synthetic oligonucleotides, and by immunological selection of clones expressing the product. The genetic mechanisms responsible for intra-strain variability of proteins II will be studied with DNA probes to variable and constant areas of the molecule. The folding of protein I will be studied with bifunctional reagents, and its secondary and tertiary structure elucidated by spectroscopic and X-ray diffraction techniques. The steps involved in pilin assembly into fully formed pili will be studied by chemical and genetic techniques. The ligand on human cells binding to gonococcal pili will be defined.