Beta-defensin 2 explained

Beta-defensin 2 (BD-2) also known as skin-antimicrobial peptide 1 (SAP1) is a peptide that in humans is encoded by the DEFB4 (defensin, beta 4) gene.[1]

Human beta-defensin-2 (hBD-2) is a cysteine-rich cationic low molecular weight antimicrobial peptide discovered in lesional skin.

Structure

hBD-2 is a protein whose primary structure is made by 64 aminoacids. At concentrations ≤2.4 mM, hBD-2 is monomeric.[2] The structure is amphiphilic with a nonuniform surface distribution of positive charge and contains several key structural elements, including a triple-stranded, antiparallel beta sheet with strands 2 and 3 in a beta hairpin conformation. The determination of other structural elements depends on the technique used. When X-ray crystallography is used an alpha helix can be observed at the N-terminal end of the protein (PDB codes:,, and). When using NMR this alpha-helix does not appear (PDB code:), however this structure was determined using a truncated version of hBD-2 which was missing the initial 4 amino acids, and may be the reason for the discrepancy.

Function

Defensins form a family of microbicidal and cytotoxic peptides made by neutrophils. Members of the defensin family are highly similar in protein sequence. Beta-defensin 2 is an antibiotic peptide which is locally regulated by inflammation.[3]

Human beta-defensin 2 is produced by a number of epithelial cells and exhibits potent antimicrobial activity against Gram-negative bacteria and Candida, but not Gram-positive S. aureus. It has been speculated that beta-defensin 2 may contribute to the infrequency of Gram-negative infections on skin and lung tissue.[4]

hBD-2 represents the first human defensin that is produced following stimulation of epithelial cells by contact with microorganisms such as P. aeruginosa or cytokines such as TNF-alpha and IL-1 beta. The HBD-2 gene and protein are locally expressed in keratinocytes associated with inflammatory skin lesions. It is intriguing to speculate that HBD-2 is a dynamic component of the local epithelial defense system of the skin and respiratory tract having a role to protect surfaces from infection, and providing a possible reason why skin and lung infections with Gram-negative bacteria are rather rare.[4]

Although this protein doesn’t have any antibacterial activity against Gram-positive bacteria, there is a study showing that there is a synergy between hBD-2 and other proteins.[5] One example of this synergistic effect is with epiP, a protein segregated by some strains of S. epidermidis. hBD2, holding hands with epiP, is capable of killing S. aureus, a Gram-positive bacteria responsible of human diseases.

Further reading

Notes and References

  1. Harder J, Bartels J, Christophers E, Schröder JM . A peptide antibiotic from human skin . Nature . 387 . 6636 . 861 . June 1997 . 9202117 . 10.1038/43088 . 4354862 . free .
  2. Sawai MV, Jia HP, Liu L, Aseyev V, Wiencek JM, McCray PB, Ganz T, Kearney WR, Tack BF . The NMR structure of human beta-defensin-2 reveals a novel alpha-helical segment . Biochemistry . 40 . 13 . 3810–3816 . April 2001 . 11300761 . 10.1021/bi002519d .
  3. Web site: Entrez Gene: DEFB4 defensin, beta 4.
  4. Schröder JM, Harder J . Human beta-defensin-2 . The International Journal of Biochemistry & Cell Biology . 31 . 6 . 645–651 . June 1999 . 10404637 . 10.1016/S1357-2725(99)00013-8 .
  5. Iwase T, Uehara Y, Shinji H, Tajima A, Seo H, Takada K, Agata T, Mizunoe Y . Staphylococcus epidermidis Esp inhibits Staphylococcus aureus biofilm formation and nasal colonization . Nature . 465 . 7296 . 346–349 . May 2010 . 20485435 . 10.1038/nature09074 . 2010Natur.465..346I . 4392908 .

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