Antimicrobial Peptide AP00524

     
 

APD ID:

AP00524

 
 

Name/Class:

Human beta defensin 2 (hBD-2; hBD2; UCSS1a; human, primates, mammals, animals; ZZHh; 3S=S; JJsn)

 
 

Source:

skin, lung, trachea epithelia, and uterus, oral (saliva); Homo sapiens

 
 

Sequence:

GIGDPVTCLKSGAICHPVFCPRRYKQIGTCGLPGTKCCKKP

 
 

Length:

41

 
 

Net charge:

7

 
 

Hydrophobic residue%:

36%

 
 

Boman Index:

0.9 kcal/mol

 
 

3D Structure:

Combine Helix and Beta structure

 
 

Method:

X-ray

 
 

SwissProt ID:

PDB ID: 1FD3   Go to PDB

 
 

Activity:

anti-Gram+ & Gram-, antiviral, antifungal, anti-HIV, Chemotactic, wound healing,

 
 

Crucial residues:

properly folded structure is required for antimicrobial activity.

 
 

Additional info:

Sequence most similar to bovine tracheal antimicrobial peptide (the first beta defensin). hBD-2 is induced and is mainly expressed under inflammatary conditions. The level of hBD-2 in human milk is in the range of 2.6-16.3 ug/ml in Latin American women (Baricelli J et al., 2014). Active against and killed E. coli, P. aeruginosa, A. baumannii, and C. albicans but show bacteriostatic effect on S. aureus. Activity is salt-sensitive. It also shows synergistic effect with LL-37 in controling group B Streptococcus, an important neonatal pathogen (Dorschner RA et al., 2003). Both hBD-2 and hBD-3 inhibit R5 and X4 types of HIV-1 infection in a dose-dependent manner (Sun et al. 2005 J Virol 79: 14318-29). MOA: Its anti-HIV-1 effect may be due to a direct inactivation of cell-free virions and inhibition viral replication after cDNA formation (Weinberg et al 2006 Adv Dent Res 19: 42-8). Dietary histone deacetylase inhibitor sulforaphane and butyrate induces HBD-2 expression in intestinal epithelial cells (Immunology 2008; 125: 241-51).

In addition, hBD-2 and hBD-3 induce chemotaxis via interactions with CCR2 (Rohrl J et al., 2010) or CCR6 expressing cells (Yang et al., 1999). IL-17A and IL-17F are most effective inducer of hBD-2 in human airway epithelial cells (Archer NK et al., 2016).

The 3 disulfide bonds are between residues 8-37, 15-30, and 20-38. The structure (one N-terminal helix and 3 beta strands) was found to be monomer in solution (Sawai MW et al 2001 Biochemistry 40:3810; PDB ID: 1E4Q) but a dimer in the crystal (Hoover DM et al 2000 J Biol Chem 275:32911; use the PDB link below (nmr+x). There are other crystal structures solved in a differnt crystal or for mutants, as well as NMR structure solved by Sawai et al. (2001), see 1FQQ. Note that there are multiple mutant structures in the PDB. You can rotate, zoom, and view the dimeric crystal structure 1FD3 here in the PDB. Such a fold can be imporant for inhibiting the Kv1.3 potassium channel (channel inhibitor). Also, its antifungal structure in complex with phosphatidylinositol 4,5-bisphosphate (PIP2) has been determined (Järvå M et al., 2018). Mutations in these sites ablate PIP2-mediated fungal growth inhibition by HBD-2. You can rotate, zoom, and view the complex crystal structure here. It also has wound healing effect (Otte JM et al., 2009). Transgenic plants: expression of this peptide in Arabidopsis thaliana reduced fungal infection (Plant Cell Rep. 2007 Aug;26(8):1391-8). APD update: 6/13/2012; 12/2013; 2/2014; 6/2014; 9/2014; 10/2016; 3/2017; 6/2017; 8/2018; 11/2018 GW.

 
       
 

Title:

A peptide antibiotic from human skin

 
 

Author:

Harder J, Bartels J, Christophers E, Schröder JM.1997

 
 

Reference:

Nature. 1997 Jun 26;387(6636):861. PubMed.

 
       

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