S100A7 (Psoriasin)--mechanism of antibacterial action in wounds.
S100A7, also called psoriasin, is a member of the S100 multigene family that is encoded in the epidermal differentiation complex on chromosome 1q21. S100A7 is highly expressed in epidermal hyperproliferative disease; however, its function is not well understood. These studies show high levels of monomer and covalently crosslinked high molecular weight S100A7 in human wound exudate and granulation tissue. Immunohistological studies suggest that this S100A7 is produced by keratinocytes surrounding the wound and is released into the wound exudate. S100A7 is also detected in keratinocyte-conditioned cell culture medium. Studies using recombinant S100A7 indicate that it adheres to and reduces E. coli survival. Mutation of the conserved carboxyl-terminal EF-hand calcium-binding motif or heat denaturation slightly reduces S100A7 antibacterial activity; however, the antibacterial activity is destroyed by protease treatment. Mutation of the zinc-binding motif, located at the C-terminus, reduces antibacterial activity; however, this reduction can be reversed by simultaneous removal of the amino terminus. This indicates the surprising finding that the central region of S100A7, including only amino acids 35-80, is sufficient for full antibacterial activity. These studies also indicate that reduced S100A7 association with bacteria is associated with reduced antibacterial activity.
Lee
Kathleen C
KC
Department of Physiology and Biophysics, Case Western Reserve University School of Medicine, Cleveland, Ohio 44106-4970, USA.
Eckert
Richard L
RL
D020816:Amino Acid Motifs / Q000502:physiology; D000595:Amino Acid Sequence; D000900:Anti-Bacterial Agents / Q000378:metabolism* / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism; D002135:Calcium-Binding Proteins / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology / Q000502:physiology*; D002478:Cells, Cultured; D004926:Escherichia coli / Q000187:drug effects / Q000502:physiology; D006097:Granulation Tissue / Q000378:metabolism; D006358:Hot Temperature; D006801:Humans; D008969:Molecular Sequence Data; D017434:Protein Structure, Tertiary; D011994:Recombinant Proteins / Q000494:pharmacology; D000075023:S100 Calcium Binding Protein A7; D009418:S100 Proteins; D014947:Wounds and Injuries / Q000378:metabolism*; D015032:Zinc / Q000378:metabolism
D000900:Anti-Bacterial Agents; D002135:Calcium-Binding Proteins; D011994:Recombinant Proteins; D000075023:S100 Calcium Binding Protein A7; D009418:S100 Proteins; C089242:S100A7 protein, human; D015032:Zinc; D002118:Calcium