Defensins Interactions

[INTRODUCTION] [TABLE OF DEFENSIN INTERACTION] [PUBLICATION LIST]



Introduction

Defensins, like all other biological molecules, bind directly to specific cellular or extracellular targets to exert their effects. The exact function of the binding interaction is sometimes unknown, so the purpose of this section is to list those defensin interactors of unknown or partially characterized biological function. This would include all proteomics experiments and some candidate-gene studies where the interaction is unexpected and cannot be satisfactorily placed into a biochemical pathway or network.

Elements to include in the section would be experimental interaction detection method (MI:0045), experimental participant identification method (MI:0661) of the interactor, interaction type (MI:0190) consisting of genetic interaction, physical interaction, and colocalization, and interactor type (MI:0313) consisting of gene, small molecule, unknown participant, and biopolymer. Future expansion of the Defensin Interactions section would remain closely aligned with the HUPO Proteomics Standards Initiative (PSI) molecular interactions (MI) ontology.




Table of Defensin Interactions

Intra-species interactions

Homo sapiens (Human)

Short Label DEFB2
Interactor CXCR4
Brief Description CXCR4 could not be visualised on the T cell membrane nor in the cells after treatment with the respective DEFBs. DEFB2 and DEFB3 were seen to bind to the cell membrane in fixed cells and were found internally in permeabilized live cells. The authors suggest that DEFB2 and DEFB3 bind to CXCR4 and induce internalization of the bound complex.
Experimental Interaction Detection Method Imaging technique: Confocal microscopy
Experimental Participant Identification Method Predetermined participant: Tag visualisation: Tag visualisation by fluorescence
Interaction Type Colocalization
Interactor Type All: Biopolymer: Protein
Literature 16672548 (2006)


Short Label DEFB2
Interactor CCR6
Brief Description CCR6 competitively displaced the CCR6 radioligand 125-iodinated LARC in the binding assay. CCR6 expressed by immature dendritic cells was involved in the cell migration in response to DEFB2.
Experimental Interaction Detection Method Biochemical: Affinity technology: Competition binding
Experimental Participant Identification Method Predetermined participant: Tag visualisation: Anti tag western blot. (assumed; data for CCR6 expression in transfected cells is not mentioned or shown.)
Interaction Type Physical interaction: Direct interaction
Interactor Type All: Biopolymer: Protein
Literature 10521347 (1999)


Short Label DEFB3 (DEFB103A)
Interactor CXCR4
Brief Description CXCR4 could not be visualised on the T cell membrane nor in the cells after treatment with the respective DEFBs. DEFB2 and DEFB3 were seen to bind to the cell membrane in fixed cells and were found internally in permeabilized live cells. The authors suggest that DEFB2 and DEFB3 bind to CXCR4 and induce internalization of the bound complex.
Experimental Interaction Detection Method Imaging technique: Confocal microscopy
Experimental Participant Identification Method Predetermined participant: Tag visualisation: Tag visualisation by fluorescence
Interaction Type Colocalization
Interactor Type All: Biopolymer: Protein
Literature 16672548 (2006)


Short Label DEFB3 (DEFB103A)
Interactor CXCR4
Brief Description CXCR4 competitively displaced the CXCR4 radioligand 125-iodinated SDF-1 in binding assay. In lymphoid and myeloid cell lines and in primary lymphocytes, DEFB3 blocked the downstream ERK1/2 phosphorylation and calcium mobilization of activated CXCR4, thus showing antagonist action. In Jurkat cells and activated human T cells, DEFB3 also showed antagonist action by reducing SDF-1-dependent chemotaxis.
Experimental Interaction Detection Method Biochemical: Affinity technology: Competition binding
Experimental Participant Identification Method Predetermined participant: Tag visualisation: Tag visualisation by fluorescence
Interaction Type Physical interaction: Direct interaction
Interactor Type All: Biopolymer: Protein
Literature 16818731 (2006)


Mus musculus (Mouse)

Short Label Cryptdin 1
Interactor Matrilysin
Brief Description Matrilysin cleaved the pro segment of Paneth cell cryptdins 1 and 15 for their activation. In vivo, matrilysin-deficient mice lacked mature cryptdins and also accumulated precursor molecules (acid-urea PAGE). In vitro, matrilysin cleaved procryptdin-1 and procryptdin-15 to produce the respective mature cryptdins, confirmed by peptide sequencing.
Experimental Interaction Detection Method Biochemical: Enzymatic study: protease assay
Experimental Participant Identification Method Predetermined participant: Tag visualisation: Anti tag western blot
Interaction Type Physical interaction: Direct interaction
Interactor Type All: Biopolymer: Protein
Literature 10506557 (1999)


Short Label Cryptdin 15
Interactor Matrilysin
Brief Description Matrilysin cleaved the pro segment of Paneth cell cryptdins 1 and 15 for their activation. In vivo, matrilysin-deficient mice lacked mature cryptdins and also accumulated precursor molecules (acid-urea PAGE). In vitro, matrilysin cleaved procryptdin-1 and procryptdin-15 to produce the respective mature cryptdins, confirmed by peptide sequencing.
Experimental Interaction Detection Method Biochemical: Enzymatic study: protease assay
Experimental Participant Identification Method Predetermined participant: Tag visualisation: Anti tag western blot
Interaction Type Physical interaction: Direct interaction
Interactor Type All: Biopolymer: Protein
Literature 10506557 (1999)


Short Label DEFB2
Interactor TLR4; Toll-like receptor 4
Brief Description DEFB2 induced the maturation of bone marrow-derived immature dendritic cells, and appeared to induce many of the same signal transduction responses as LPS. The authors deemed it unlikely that the effects of DEFB2 were due to contaminating LPS because the amount of endotoxin in the purified DEFB2 protein was well below the threshold level of 1 ng/mL LPS. The LPS receptor is previously known to be TLR4. Immature dendritic cells from TLR4-mutated or -KO mice failed to mature when treated with DEFB2, and HEK293 cells transiently transfected with the reporter gene construct TLR4-Luc showed high luciferase activity when treated with DEFB2.
Experimental Interaction Detection Method Biochemical
Experimental Participant Identification Method Predetermined participant: Tag visualisation: Anti tag western blot. (assumed; data for both DEFB2 and TLR4 expression in transfected cells is not mentioned or shown.)
Interaction Type Physical interaction: Direct interaction
Interactor Type All: Biopolymer: Protein
Literature 12411706 (2002)


Inter-species interactions

Plant-fungus interactions

Short Label (species) Psd1 (Pisum sativum; garden pea)
Interactor (species) Cyclin F (Neurospora crassa)
Brief Description Psd1 was the bait in a yeast two-hybrid screen of Neurospora crassa cDNA, and captured a prey that was found to have cyclin-like F-box and WD-repeat domains. The prey was identified as cyclin F, a nuclear protein. In vitro, the reciprocal GST pulldown assay confirmed this interaction and supported the prey identification. In vivo fluorescence microscopy further supported the interaction by showing nuclear localization of Psd1, in another fungus Fusarium solani. Flow cytometry analysis of N. crassa germinating conidia treated with Psd1 suggested that Psd1 interfered with nuclear division in the cell cycle.
Experimental Interaction Detection Method Protein complementation assay: Transcriptional complementation assay: Two hybrid
Experimental Participant Identification Method Nucleotide sequence identification: Full identification by sequencing
Interaction Type Physical interaction: Direct interaction
Interactor Type All: Biopolymer: Protein
Literature 17240982 (2006)





Publication List




2007

Antifungal Pisum sativum defensin 1 interacts with Neurospora crassa cyclin F related to the cell cycle.
Lobo DS, Pereira IB, Fragel-Madeira L, Medeiros LN, Cabral LM, Faria J, Bellio M, Campos RC, Linden R, Kurtenbach E Biochemistry 2007 Jan;46 (4):987-96
PMID: 17240982



2006

Cutting edge: human beta defensin 3--a novel antagonist of the HIV-1 coreceptor CXCR4.
Feng Z, Dubyak GR, Lederman MM, Weinberg A J. Immunol. 2006 Jul;177 (2):782-6
PMID: 16818731

Role of human beta-defensins in HIV infection.
Adv. Dent. Res. 2006 ;19 (1):42-8
PMID: 16672548



2002

Toll-like receptor 4-dependent activation of dendritic cells by beta-defensin 2.
Biragyn A, Ruffini PA, Leifer CA, Klyushnenkova E, Shakhov A, Chertov O, Shirakawa AK, Farber JM, Segal DM, Oppenheim JJ, Kwak LW Science 2002 Nov;298 (5595):1025-9
PMID: 12411706



1999

Beta-defensins: linking innate and adaptive immunity through dendritic and T cell CCR6.
Yang D, Chertov O, Bykovskaia SN, Chen Q, Buffo MJ, Shogan J, Anderson M, Schroder JM, Wang JM, Howard OM, Oppenheim JJ Science 1999 Oct;286 (5439):525-8
PMID: 10521347

Regulation of intestinal alpha-defensin activation by the metalloproteinase matrilysin in innate host defense.
Science 1999 Oct;286 (5437):113-7
PMID: 10506557