Hemoglobin digestion in blood-feeding ticks: mapping a multipeptidase pathway by functional proteomics.
Hemoglobin digestion is an essential process for blood-feeding parasites. Using chemical tools, we deconvoluted the intracellular hemoglobinolytic cascade in the tick Ixodes ricinus, a vector of Lyme disease and tick-borne encephalitis. In tick gut tissue, a network of peptidases was demonstrated through imaging with specific activity-based probes and activity profiling with peptidic substrates and inhibitors. This peptidase network is induced upon blood feeding and degrades hemoglobin at acidic pH. Selective inhibitors were applied to dissect the roles of the individual peptidases and to determine the peptidase-specific cleavage map of the hemoglobin molecule. The degradation pathway is initiated by endopeptidases of aspartic and cysteine class (cathepsin D supported by cathepsin L and legumain) and is continued by cysteine amino- and carboxy-dipeptidases (cathepsins C and B). The identified enzymes are potential targets to developing novel anti-tick vaccines.
Horn
Martin
M
Institute of Organic Chemistry and Biochemistry, Academy of Sciences of the Czech Republic, 16610 Praha, Czech Republic.
Nussbaumerová
Martina
M
Sanda
Miloslav
M
Kovárová
Zuzana
Z
Srba
Jindrich
J
Franta
Zdenek
Z
Sojka
Daniel
D
Bogyo
Matthew
M
Caffrey
Conor R
CR
Kopácek
Petr
P
Mares
Michael
M
D000595:Amino Acid Sequence; D000818:Animals; D020134:Catalytic Domain; D002401:Cathepsin B / Q000378:metabolism; D020789:Cathepsin C / Q000378:metabolism; D002402:Cathepsin D / Q000378:metabolism; D056668:Cathepsin L / Q000378:metabolism; D003546:Cysteine Endopeptidases / Q000378:metabolism; D010450:Endopeptidases / Q000378:metabolism*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006454:Hemoglobins / Q000737:chemistry / Q000378:metabolism*; D006863:Hydrogen-Ion Concentration; D018884:Ixodes / Q000201:enzymology*; D008969:Molecular Sequence Data; D040901:Proteomics / Q000379:methods*; D000099240:Asparaginyl Endopeptidase
D002401:Cathepsin B; D020789:Cathepsin C; D002402:Cathepsin D; D056668:Cathepsin L; D003546:Cysteine Endopeptidases; D010450:Endopeptidases; D004791:Enzyme Inhibitors; D006454:Hemoglobins; D000099240:Asparaginyl Endopeptidase