Beta-defensin 2

DEFB4A
Available structures PDB Human UniProt search: PDBe RCSB List of PDB id codes 1E4Q, 1FD3, 1FD4, 1FQQ
Identifiers
Aliases	DEFB4A, BD-2, DEFB-2, DEFB102, DEFB2, DEFB4, HBD-2, SAP1, Beta-defensin 2, defensin beta 4A
External IDs	HomoloGene: 122147 GeneCards: DEFB4A
Gene ontology Molecular function • protein binding • CCR6 chemokine receptor binding Cellular component • Golgi lumen • extracellular region • extracellular space Biological process • G-protein coupled receptor signaling pathway • defense response • innate immune response • immune response • chemotaxis • defense response to Gram-negative bacterium • defense response to bacterium • defense response to Gram-positive bacterium Sources:Amigo / QuickGO
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_001192195.1 NP_004933.1	n/a
Location (UCSC)	Chr 8: 7.89 – 7.9 Mb	n/a
PubMed search	[1]	n/a
Wikidata

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.^[2]

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.^[3] 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

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.^[4]

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.^[5]

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.^[5]

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.^[6] 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

Further reading

PDB gallery
1e4q: SOLUTION STRUCTURE OF THE HUMAN DEFENSIN HBD-2  1fd3: HUMAN BETA-DEFENSIN 2  1fd4: HUMAN BETA-DEFENSIN 2  1fqq: SOLUTION STRUCTURE OF HUMAN BETA-DEFENSIN-2