Guanylyl cyclases with the topology of mammalian adenylyl cyclases and an N-terminal P-type ATPase-like domain in Paramecium, Tetrahymena and Plasmodium

We cloned a guanylyl cyclase of 280 kDa from the ciliate Paramecium which has an N‐terminus similar to that of a P‐type ATPase and a C‐terminus with a topology identical to mammalian adenylyl cyclases. Respective signature sequence motifs are conserved in both domains. The cytosolic catalytic C1a an...

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Bibliographic Details
Published in:The EMBO journal 1999-08, Vol.18 (15), p.4222-4232
Main Authors: Linder, Jürgen U., Engel, Peter, Reimer, Andreas, Krüger, Thomas, Plattner, Helmut, Schultz, Anita, Schultz, Joachim E.
Format: Article
Language:English
Subjects:
adenylyl cyclase
Amino Acid Sequence
Animals
Apicomplexa
Base Sequence
cGMP
Ciliophora
Cloning, Molecular
DNA Primers
Guanylate Cyclase - chemistry
Guanylate Cyclase - genetics
guanylyl cyclase
Humans
Isoenzymes - chemistry
Isoenzymes - genetics
Mammals
Microscopy, Immunoelectron
Molecular Sequence Data
Mutagenesis, Site-Directed
Paramecium
Paramecium - enzymology
Paramecium - genetics
Paramecium - ultrastructure
Plasmodium
Plasmodium - enzymology
Plasmodium - genetics
Protein Conformation
Sequence Homology, Amino Acid
Tetrahymena
Tetrahymena - enzymology
Tetrahymena - genetics
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Summary:We cloned a guanylyl cyclase of 280 kDa from the ciliate Paramecium which has an N‐terminus similar to that of a P‐type ATPase and a C‐terminus with a topology identical to mammalian adenylyl cyclases. Respective signature sequence motifs are conserved in both domains. The cytosolic catalytic C1a and C2a segments of the cyclase are inverted. Genes coding for topologically identical proteins with substantial sequence similarities have been cloned from Tetrahymena and were detected in sequences from Plasmodium deposited by the Malaria Genome Project. After 99 point mutations to convert the Paramecium TAA/TAG‐Gln triplets to CAA/CAG, together with partial gene synthesis, the gene from Paramecium was heterologously expressed. In Sf9 cells, the holoenzyme is proteolytically processed into the two domains. Immunocytochemistry demonstrates expression of the protein in Paramecium and localizes it to cell surface membranes. The data provide a novel structural link between class III adenylyl and guanylyl cyclases and imply that the protozoan guanylyl cyclases evolved from an ancestral adenylyl cyclase independently of the mammalian guanylyl cyclase isoforms. Further, signal transmission in Ciliophora (Paramecium, Tetrahymena) and in the most important endoparasitic phylum Apicomplexa (Plasmodium) is, quite unexpectedly, closely related.
ISSN:0261-4189
1460-2075
1460-2075
DOI:10.1093/emboj/18.15.4222