2MCR

Solution structure of ShK-like immunomodulatory peptide from Brugia malayi (filarial worm)

Summary for 2MCR

• Entry DOI: 10.2210/pdb2mcr/pdb
• Related: 1ROO 2K72
• NMR Information: BMRB: 19450
• Descriptor: Probable zinc metalloproteinase, putative (1 entity in total)
• Functional Keywords: worms, bmk1, shk-like peptide, kv1.3, immune system
• Biological source: Brugia malayi
• Total number of polymer chains: 1
• Total formula weight: 4182.89

Authors

Chhabra, S.,Swarbrick, J.D.,Pennington, M.W.,Chang, S.C.,Norton, R.S. (deposition date: 2013-08-22, release date: 2014-07-02, Last modification date: 2024-11-27)

Primary citation

Chhabra, S.,Chang, S.C.,Nguyen, H.M.,Huq, R.,Tanner, M.R.,Londono, L.M.,Estrada, R.,Dhawan, V.,Chauhan, S.,Upadhyay, S.K.,Gindin, M.,Hotez, P.J.,Valenzuela, J.G.,Mohanty, B.,Swarbrick, J.D.,Wulff, H.,Iadonato, S.P.,Gutman, G.A.,Beeton, C.,Pennington, M.W.,Norton, R.S.,Chandy, K.G.
Kv1.3 channel-blocking immunomodulatory peptides from parasitic worms: implications for autoimmune diseases.
Faseb J., 28:3952-3964, 2014

PubMed Abstract: The voltage-gated potassium (Kv) 1.3 channel is widely regarded as a therapeutic target for immunomodulation in autoimmune diseases. ShK-186, a selective inhibitor of Kv1.3 channels, ameliorates autoimmune diseases in rodent models, and human phase 1 trials of this agent in healthy volunteers have been completed. In this study, we identified and characterized a large family of Stichodactyla helianthus toxin (ShK)-related peptides in parasitic worms. Based on phylogenetic analysis, 2 worm peptides were selected for study: AcK1, a 51-residue peptide expressed in the anterior secretory glands of the dog-infecting hookworm Ancylostoma caninum and the human-infecting hookworm Ancylostoma ceylanicum, and BmK1, the C-terminal domain of a metalloprotease from the filarial worm Brugia malayi. These peptides in solution adopt helical structures closely resembling that of ShK. At doses in the nanomolar-micromolar range, they block native Kv1.3 in human T cells and cloned Kv1.3 stably expressed in L929 mouse fibroblasts. They preferentially suppress the proliferation of rat CCR7(-) effector memory T cells without affecting naive and central memory subsets and inhibit the delayed-type hypersensitivity (DTH) response caused by skin-homing effector memory T cells in rats. Further, they suppress IFNγ production by human T lymphocytes. ShK-related peptides in parasitic worms may contribute to the potential beneficial effects of probiotic parasitic worm therapy in human autoimmune diseases.

PubMed: 24891519
DOI: 10.1096/fj.14-251967

Experimental method

SOLUTION NMR