Trypanosoma cruzi adenylyl cyclase is encoded by a complex multigene family

The parasitic protozoan Trypanosoma cruzi undergoes several differentiation events during its life cycle. Some of these transitions are thought to inv olve activation of adenylyl cyclase via the binding of peptide ligands to t he cell surface, Here we describe the characterisation of the adenylyl cycl ase gene family of T. cruzi. Two complete genes and one pseudogene have bee n sequenced. The protein products appear to have a large extracellular doma in, a single transmembrane helix and a cytosolic catalytic domain. The aden ylyl cyclase genes are present on at least six chromosomes and are scattere d rather than clustered. They form a large polymorphic family in which the extracellular domain is particularly variable. An Escherichia coli adenylyl cyclase mutant could be complemented by expression of the catalytic domain of the T. cruzi enzyme. The recombinant protein had adenylyl cyclase activ ity in vitro, which was enhanced by increasing concentrations of divalent c ations (Mn2+ > Mg2+). This constitutively active recombinant protein will b e a useful tool for dissecting the catalytic mechanism of adenylyl cyclase. (C) 1999 Elsevier Science B.V. All rights reserved.