The Isolation and Characterization of a Novel Corticostatin/Defensin-like Peptide from the Kidney

Bateman, Andrew; Macleod, John; Lembessis, Peter; Hu, Jing; Esch, Frederick; Solomon, Samuel

doi:10.1074/jbc.271.18.10654

Cited by 55 publications

(41 citation statements)

References 39 publications

(36 reference statements)

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“…The hydrophobic patch is not conserved, and with a global charge of ϩ1, RK-1 is not really cationic. RK-1 is active against E. coli at rather high concentrations (15-150 g/ml) but can also activate Ca 2ϩ channels in vitro (40). This means that, in addition to being antibacterial, it bears some toxin properties.…”

Section: Table II Effect Of Sodium and Magnesium Chloride On Sphe-2 Amentioning

confidence: 99%

Solution Structure of Spheniscin, a β-Defensin from the Penguin Stomach

Landon

Thouzeau

Labbé

et al. 2004

Journal of Biological Chemistry

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Recently two ␤-defensins, named spheniscins, have been isolated from the stomach content of the king penguin (Aptenodytes patagonicus), which is capable of preserving food for several weeks during egg incubation (Thouzeau, C., Le Maho, Y., Froget, G., Sabatier, L., Le Bohec, C., Hoffmann, J. A., and Bulet, P. (2003) J. Biol. Chem. 278, 51053-51058). It has been proposed that, in combination with other antimicrobial peptides, spheniscins may be involved in this long term preservation of food in the bird's stomach. To draw some structure/ function features, the three-dimensional structure in aqueous solution of the most abundant spheniscin (Sphe-2) was determined by two-dimensional NMR and molecular modeling techniques. The overall fold of Sphe-2 includes a three-stranded antiparallel ␤-sheet stabilized by three disulfide bridges with a pairing typical of ␤-defensins. In addition, the N-terminal segment shows helical features on most structures. Sphe-2 is highly cationic, and its surface displays a hydrophobic patch. Comparative modeling revealed that this patch is preserved in avian defensins. The activity of Sphe-2 against a pathogenic Gram-positive strain was retained in vitro in the conditions of osmolarity found in penguin stomach content and also in different salt concentrations and compositions up to those reported for seawater. Comparison with structurally related mammalian ␤-defensins showed that the hydrophobic patch is not preserved in mammalian ␤-defensins and that the high cationicity of Sphe-2 is presumably the critical factor for its retained activity in high salt concentrations. Such peculiarities, in addition to a broad activity spectrum, suggest that penguin defensins may represent interesting probes for the design of highly efficient antibiotics to fight off pathogens that develop in relatively salt-rich body fluids.During the final stage of egg incubation in king penguins (Aptenodytes patagonicus), the male can preserve undigested food in the stomach for several weeks (1). This ensures survival of the newly hatched chick in the event that the return of the foraging female from the sea is delayed. In accordance with the characterization of stress-induced bacteria (2), a previous study has demonstrated that numerous antimicrobial activities exist in preserved stomach contents (3). Two antimicrobial peptides have been isolated and fully characterized, namely spheniscin-1 and -2 (Sphe-1/pBD-1 and Sphe-2/pBD-2).1 The two forms of spheniscins differ by a single residue, His 14 , in Sphe-1 versus Arg 14 in Sphe-2. A data bank search revealed that spheniscins are members of the well known defensin family.Defensins are small (3-5 kDa) cationic antimicrobial peptides that are part of the innate immunity of vertebrates (4, 5), invertebrates (6), and plants (7). In vertebrates, defensins can be divided into ␣-, ␤-, and -defensin subfamilies. The unusual -defensin, which is a circular peptide, was initially isolated from rhesus macaque (8). Recently a pseudogene coding for a homologue, named retrocyclin, wa...

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Section: Table II Effect Of Sodium and Magnesium Chloride On Sphe-2 Amentioning

confidence: 99%

Solution Structure of Spheniscin, a β-Defensin from the Penguin Stomach

Landon

Thouzeau

Labbé

et al. 2004

Journal of Biological Chemistry

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“…It is now becoming clear that defensins constitute a primary defense system of the host. The activity of a few K-defensins as speci¢c antagonists of adrenocorticotropin has led to their classi¢cation as the corticostatin/defensin family [7]. This review focuses on the current status of defensins in terms of their wide-spread occurrence, their molecular, cellular and structural biology, structure^function relationships, mechanism of their microbicidal activity and future research paradigms.…”

Section: Introductionmentioning

confidence: 99%

Current status of defensins and their role in innate and adaptive immunity

Raj

2002

FEMS Microbiology Letters

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Naturally occurring antimicrobial cationic polypeptides play a major role in innate and adaptive immunity. These polypeptides are found to be either linear and unstructured or structured through disulfide bonds. Among the structured antimicrobial polypeptides, defensins comprise a family of cysteine-rich cationic polypeptides that contribute significantly to host defense against the invasion of microorganisms in animals, humans, insects and plants. Their wide-spread occurrence in various tissues of these diverse organisms, and their importance in innate and adaptive immunity have led to their identification, isolation and characterization. A large volume of literature is available on defensins' occurrence, structural characterization, gene expression and regulation under normal and pathological conditions. Much has also been published regarding their antimicrobial, antiviral and chemoattractive properties, and their molecular and cellular interactions. In this review, we describe the current status of our knowledge of defensins with respect to their molecular, cellular and structural biology, their role in host defense, future research paradigms and the possibility of their utilization as a new class of non-toxic antimicrobial agents and immuno-modulators. ß

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“…Sequence analysis of most known mammalian ␣-defensins indicates that Arg is strongly selected over Lys by a ratio of ϳ9:1, with few exceptions such as corticostatin/defensin-like peptides (RK-1 and RK-2) expressed in the rabbit kidney (24,25). In humans, none of the six ␣-defensins contain Lys in their mature domain sequences.…”

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confidence: 99%

Toward Understanding the Cationicity of Defensins

Zou

Leeuw

et al. 2007

Journal of Biological Chemistry

127

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Human defensins are a family of small antimicrobial proteins found predominantly in leukocytes and epithelial cells that play important roles in the innate and adaptive immune defense against microbial infection. The most distinct molecular feature of defensins is cationicity, manifested by abundant Arg and/or Lys residues in their sequences. Sequence analysis indicates that Arg is strongly selected over Lys in ␣-defensins but not in ␤-defensins. To understand this Arg/Lys disparity in defensins, we chemically synthesized human ␣-defensin 1 (HNP1) and several HNP1 analogs where three Arg residues were replaced by each of the following six ␣-amino acids: Lys, ornithine (Orn), diaminobutyric acid (Dab), diaminopropionic acid (Dap), N,N-dimethyl-Lys ( diMe Lys), and homo-Arg ( homo Arg). In addition, we prepared human ␤-defensin 1 (hBD1) and Lys3 Arg hBD1 in which all four Lys residues were substituted for Arg. Bactericidal activity assays revealed the following. 1) Arg-containing HNP1 and Lys3 Arg hBD1 are functionally better than Lys-HNP1 and hBD1, respectively; the difference between Arg and Lys is more evident in the ␣-defensin than in the ␤-defensin and is more evident at low salt concentrations than at high salt concentrations. 2) For HNP1, the Arg/Lys disparity is much more pronounced with Staphylococcus aureus than with Escherichia coli, and the Arg-rich HNP1 kills bacteria faster than its Lys-rich analog. 3) Arg and Lys appear to have optimal chain lengths for bacterial killing as shortening Lys or lengthening Arg in HNP1 invariably becomes functionally deleterious. Our findings provide insights into the Arg/Lys disparity in defensins, and shed light on the cationicity of defensins with respect to their antimicrobial activity and specificity.

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The Isolation and Characterization of a Novel Corticostatin/Defensin-like Peptide from the Kidney

Cited by 55 publications

References 39 publications

Solution Structure of Spheniscin, a β-Defensin from the Penguin Stomach

Solution Structure of Spheniscin, a β-Defensin from the Penguin Stomach

Current status of defensins and their role in innate and adaptive immunity

Toward Understanding the Cationicity of Defensins

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