PRP8 intein in Ajellomycetaceae family pathogens: sequence analysis, splicing evaluation and homing endonuclease activity.
Inteins are intervening sequences that are transcribed and translated with flanking host protein sequences and then self-excised by protein splicing. Bi-functional inteins also contain a homing endonuclease responsible for their genetic mobility. The PRP8 intein, the most widespread among fungi, occurs in important pathogens such as Histoplasma capsulatum and Paracoccidioides brasiliensis, from the Ajellomycetaceae family. Herein, we describe the bi-functional PRP8 intein in two other Ajellomycetacean pathogens, Blastomyces dermatitidis and Emmonsia parva. Sequence analysis and experimental evidence suggest that the homing endonuclease from PbrPRP8 is inactive. The splicing activity of the PRP8 intein from the B. dermatitidis, E. parva and P. brasiliensis species complex was demonstrated in a non-native protein context in Escherichia coli. Since the PRP8 intein is located in a functionally essential nuclear protein, it can be considered a promising therapeutic target for anti-fungal drugs, because inhibition of intein splicing should inhibit proliferation of intein-containing pathogens.
Theodoro
Raquel Cordeiro
RC
Department of Microbiology and Immunology, Institute of Biosciences, UNESP, Botucatu, SP, Brazil.
Volkmann
Gerrit
G
Liu
Xiang-Qin
XQ
Bagagli
Eduardo
E
D000595:Amino Acid Sequence; D001758:Blastomyces / Q000201:enzymology* / Q000235:genetics / Q000378:metabolism; D002912:Chrysosporium / Q000201:enzymology* / Q000235:genetics / Q000378:metabolism; D016000:Cluster Analysis; D004720:Endonucleases / Q000235:genetics* / Q000378:metabolism*; D004926:Escherichia coli / Q000235:genetics; D005656:Fungal Proteins / Q000235:genetics / Q000378:metabolism; D047668:Inteins / Q000235:genetics*; D008969:Molecular Sequence Data; D010802:Phylogeny; D019154:Protein Splicing; D016415:Sequence Alignment; D017421:Sequence Analysis
D005656:Fungal Proteins; D004720:Endonucleases