Zinc-reversible antimicrobial activity of recombinant calprotectin (migration inhibitory factor-related proteins 8 and 14).
Recombinant calprotectin, consisting of 2 individual peptide chains also called migration inhibitory factor-related protein (MRP)-8 and MRP14, was tested for antimicrobial activity in a Candida albicans growth inhibition assay. Both chains contain HEXXH zinc-binding sites and might be expected to manifest zinc-reversible, antimicrobial activity similar to that of native calprotectin. When tested alone, neither MRP8 nor MRP14 showed activity in the Candida growth assay. A synthetic 20-amino acid peptide containing the HEXXH sequence of MRP14, along with a nearby HHH sequence, was also inactive in this assay. However, equimolar concentrations of MRP8 and MRP14 demonstrated a potent growth inhibitory effect that was reversible by 30 microM zinc. Truncated MRP14 (missing the C-terminal GHHHKPGLGEGTP tail) used in combination with MRP8 demonstrated zinc-reversible activity that was somewhat less than that with complete MRP14. These results suggest that intact calprotectin, consisting of a heterodimer of MRP8 and MRP14, is necessary to form a zinc-binding site capable of inhibiting microbial growth.
Sohnle
P G
PG
Research Service, Veterans Affairs Medical Center, Milwaukee, WI 53295, USA. psohnle@mcw.edu
Hunter
M J
MJ
Hahn
B
B
Chazin
W J
WJ
D000595:Amino Acid Sequence; D000935:Antifungal Agents / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000494:pharmacology*; D000943:Antigens, Differentiation / Q000737:chemistry / Q000494:pharmacology; D002135:Calcium-Binding Proteins / Q000737:chemistry / Q000494:pharmacology; D040501:Calgranulin A; D040502:Calgranulin B; D002176:Candida albicans / Q000187:drug effects* / Q000254:growth & development; D039841:Leukocyte L1 Antigen Complex; D008562:Membrane Glycoproteins / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000494:pharmacology*; D008826:Microbial Sensitivity Tests; D019006:Neural Cell Adhesion Molecules / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000494:pharmacology*; D011994:Recombinant Proteins / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000494:pharmacology; D009418:S100 Proteins / Q000737:chemistry / Q000494:pharmacology; D013329:Structure-Activity Relationship; D015032:Zinc / Q000494:pharmacology*
D000935:Antifungal Agents; D000943:Antigens, Differentiation; D002135:Calcium-Binding Proteins; D040501:Calgranulin A; D040502:Calgranulin B; D039841:Leukocyte L1 Antigen Complex; D008562:Membrane Glycoproteins; D019006:Neural Cell Adhesion Molecules; D011994:Recombinant Proteins; D009418:S100 Proteins; D015032:Zinc