Beta-defensin 2

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Defensin, beta 4A
Protein DEFB4 PDB 1e4q.png
PDB rendering based on 1e4q.
Available structures
PDB Ortholog search: PDBe, RCSB
Identifiers
Symbols DEFB4A ; BD-2; DEFB-2; DEFB102; DEFB2; DEFB4; HBD-2; SAP1
External IDs OMIM602215 HomoloGene122147 GeneCards: DEFB4A Gene
Orthologs
Species Human Mouse
Entrez 1673 n/a
Ensembl ENSG00000171711 n/a
UniProt O15263 n/a
RefSeq (mRNA) NM_004942 n/a
RefSeq (protein) NP_004933 n/a
Location (UCSC) Chr 8:
7.27 – 7.27 Mb
n/a
PubMed search [1] n/a

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 recently discovered in lesional skin.

Structure[edit]

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 C-terminal end of the protein (PDB code: 1fd3). When using NMR this alpha-helix does not appear (PDB code: 1e4q).

Function[edit]

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.

References[edit]

  1. ^ Harder J, Bartels J, Christophers E, Schroder JM (Jul 1997). "A peptide antibiotic from human skin". Nature 387 (6636): 861. doi:10.1038/43088. PMID 9202117. 
  2. ^ Sawai MV, Jia HP, Liu L, Aseyev V, Wiencek JM, McCray PB Jr, Ganz T, Kearney WR, Tack BF.(2001) (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. 
  3. ^ "Entrez Gene: DEFB4 defensin, beta 4". 
  4. ^ a b Schröder JM, Harder J (June 1999). "Human beta-defensin-2". Int. J. Biochem. Cell Biol. 31 (6): 645–51. doi:10.1016/S1357-2725(99)00013-8. PMID 10404637. 
  5. ^ Tadayuki Iwase, Yoshio Uehara, Hitomi Shinji, Akiko Tajima, Hiromi Seo, Koji Takada, Toshihiko Agata Yoshimitsu Mizunoe (2010) (2010). ""Staphylococcus epidermidis Esp inhibits Staphylococcus aureus biofilm formation and nasal colonization".". Nature. 465 (7296): 346–349. doi:10.1038/nature09074. PMID 20485435. 

Further reading[edit]