Denatured human alpha-defensin attenuates the bactericidal activity and the stability against enzymatic digestion.
alpha-Defensin is an antimicrobial peptide which plays an important role in innate immunity. Human defensin (HD)-5 is stored in the Paneth cells of the small intestine as a pro-form and is cleaved by trypsin, which is co-secreted from the Paneth cell granules. The mature HD-5 is protected from further digestion by the proteolysis enzyme. We generated both recombinant HD-5 and proHD-5, and the reduced form of each peptide in order to determine their physiological roles of the disulfide bonds. The reduced proHD-5 attenuated the bactericidal activity and the stability against the trypsin digestion. Human defensin was protected from the enzymatic degradation by disulfide bridges. We further purified the HD-5 with a disulfide variation in the small intestine of Crohn's disease patients. The HD-5 was sensitive to the trypsin treatment. These observations evidently predict that a defensin deficiency may be caused by a disulfide disorder in the disease.
Tanabe
Hiroki
H
Division of Gastroenterology and Hematology/Oncology, Department of Medicine, Asahikawa Medical College, Japan. tant@asahikawa-med.ac.jp
Ayabe
Tokiyoshi
T
Maemoto
Atsuo
A
Ishikawa
Chisato
C
Inaba
Yuhei
Y
Sato
Ryu
R
Moriichi
Kentaro
K
Okamoto
Kotaro
K
Watari
Jiro
J
Kono
Toru
T
Ashida
Toshifumi
T
Kohgo
Yutaka
Y
D000595:Amino Acid Sequence; D000900:Anti-Bacterial Agents / Q000737:chemistry / Q000494:pharmacology; D003424:Crohn Disease / Q000378:metabolism; D004220:Disulfides / Q000378:metabolism; D006801:Humans; D007082:Ileum / Q000378:metabolism; D008969:Molecular Sequence Data; D010455:Peptides / Q000737:chemistry / Q000494:pharmacology; D011489:Protein Denaturation; D011498:Protein Precursors / Q000737:chemistry / Q000494:pharmacology / Q000502:physiology; D011499:Protein Processing, Post-Translational; D012486:Salmonella typhimurium / Q000187:drug effects; D014357:Trypsin / Q000378:metabolism; D023084:alpha-Defensins / Q000737:chemistry / Q000494:pharmacology / Q000502:physiology*
D000900:Anti-Bacterial Agents; D004220:Disulfides; D010455:Peptides; D011498:Protein Precursors; D023084:alpha-Defensins; D014357:Trypsin