Beta-defensin 2

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DEFB4B
Available structures
PDBHuman UniProt search: PDBe RCSB
Identifiers
AliasesDEFB4B, DEFB4P, defensin beta 4B
External IDsHomoloGene: 122147 GeneCards: DEFB4B
Orthologs
SpeciesHumanMouse
Entrez

100289462

n/a

Ensembl

ENSG00000177257
ENSG00000275444
ENSG00000285433

n/a

UniProt

O15263

n/a

RefSeq (mRNA)

NM_001205266

n/a

RefSeq (protein)

NP_001192195
NP_004933

n/a

Location (UCSC)Chr 8: 7.41 – 7.42 Mbn/a
PubMed search[2]n/a
Wikidata
View/Edit Human

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.[3]

Human beta-defensin-2 (hBD-2) is a cysteine-rich cationic low molecular weight antimicrobial peptide recently 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.[4] 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: 1fd3​,1fd4​, and 6cs9​). When using NMR this alpha-helix does not appear (PDB code: 1e4q​), 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.[5]

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.[6]

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.[6]

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.[7] 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.

References

  1. ^ a b c ENSG00000275444, ENSG00000285433 GRCh38: Ensembl release 89: ENSG00000177257, ENSG00000275444, ENSG00000285433 – Ensembl, May 2017
  2. ^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  3. ^ Harder J, Bartels J, Christophers E, Schröder JM (June 1997). "A peptide antibiotic from human skin". Nature. 387 (6636): 861. doi:10.1038/43088. PMID 9202117. S2CID 4354862.
  4. ^ Sawai MV, Jia HP, Liu L, Aseyev V, Wiencek JM, McCray PB, Ganz T, Kearney WR, Tack BF (April 2001). "The NMR structure of human beta-defensin-2 reveals a novel alpha-helical segment". Biochemistry. 40 (13): 3810–3816. doi:10.1021/bi002519d. PMID 11300761.
  5. ^ "Entrez Gene: DEFB4 defensin, beta 4".
  6. ^ a b Schröder JM, Harder J (June 1999). "Human beta-defensin-2". The International Journal of Biochemistry & Cell Biology. 31 (6): 645–651. doi:10.1016/S1357-2725(99)00013-8. PMID 10404637.
  7. ^ Iwase T, Uehara Y, Shinji H, Tajima A, Seo H, Takada K, Agata T, Mizunoe Y (May 2010). "Staphylococcus epidermidis Esp inhibits Staphylococcus aureus biofilm formation and nasal colonization". Nature. 465 (7296): 346–349. Bibcode:2010Natur.465..346I. doi:10.1038/nature09074. PMID 20485435. S2CID 4392908.

External links

Further reading

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