7C31

Crystal structure of the grapevine defensin VvK1

Summary for 7C31

• Entry DOI: 10.2210/pdb7c31/pdb
• Descriptor: Knot1 domain-containing protein (2 entities in total)
• Functional Keywords: cysteine-rich, antimicrobial, antifungal, immunomodulatory, plant defensin, antimicrobial protein
• Biological source: Vitis vinifera (Grape)
• Total number of polymer chains: 2
• Total formula weight: 10476.32

Authors

Chen, M.W.,Chang, S.C.,Chandy, K.G.,Luo, D. (deposition date: 2020-05-10, release date: 2020-09-16, Last modification date: 2024-10-16)

Primary citation

Ong, S.T.,Bajaj, S.,Tanner, M.R.,Chang, S.C.,Krishnarjuna, B.,Ng, X.R.,Morales, R.A.V.,Chen, M.W.,Luo, D.,Patel, D.,Yasmin, S.,Ng, J.J.H.,Zhuang, Z.,Nguyen, H.M.,El Sahili, A.,Lescar, J.,Patil, R.,Charman, S.A.,Robins, E.G.,Goggi, J.L.,Tan, P.W.,Sadasivam, P.,Ramasamy, B.,Hartimath, S.V.,Dhawan, V.,Bednenko, J.,Colussi, P.,Wulff, H.,Pennington, M.W.,Kuyucak, S.,Norton, R.S.,Beeton, C.,Chandy, K.G.
Modulation of Lymphocyte Potassium Channel KV1.3 by Membrane-Penetrating, Joint-Targeting Immunomodulatory Plant Defensin.
Acs Pharmacol Transl Sci, 3:720-736, 2020

PubMed Abstract: We describe a cysteine-rich, membrane-penetrating, joint-targeting, and remarkably stable peptide, EgK5, that modulates voltage-gated K1.3 potassium channels in T lymphocytes by a distinctive mechanism. EgK5 enters plasma membranes and binds to K1.3, causing current run-down by a phosphatidylinositol 4,5-bisphosphate-dependent mechanism. EgK5 exhibits selectivity for K1.3 over other channels, receptors, transporters, and enzymes. EgK5 suppresses antigen-triggered proliferation of effector memory T cells, a subset enriched among pathogenic autoreactive T cells in autoimmune disease. PET-CT imaging with F-labeled EgK5 shows accumulation of the peptide in large and small joints of rodents. In keeping with its arthrotropism, EgK5 treats disease in a rat model of rheumatoid arthritis. It was also effective in treating disease in a rat model of atopic dermatitis. No signs of toxicity are observed at 10-100 times the dose. EgK5 shows promise for clinical development as a therapeutic for autoimmune diseases.

PubMed: 32832873
DOI: 10.1021/acsptsci.0c00035

Experimental method

X-RAY DIFFRACTION (1.3 Å)