3EB3

Voltage-dependent K+ channel beta subunit (W121A) in complex with cortisone

Summary for 3EB3

• Entry DOI: 10.2210/pdb3eb3/pdb
• Related: 1exb 1qrq 3EAU 3EB4
• Descriptor: Voltage-gated potassium channel subunit beta-2, NADPH DIHYDRO-NICOTINAMIDE-ADENINE-DINUCLEOTIDE PHOSPHATE, 17,21-DIHYDROXYPREGNA-1,4-DIENE-3,11,20-TRIONE, ... (4 entities in total)
• Functional Keywords: kvbeta, cortisone, interface, cytoplasm, ion transport, ionic channel, nadp, phosphoprotein, potassium, potassium transport, transport, voltage-gated channel, transport protein, oxidoreductase
• Biological source: Rattus norvegicus (brown rat,rat,rats)
• Cellular location: Cytoplasm (Potential): P62483
• Total number of polymer chains: 1
• Total formula weight: 37560.91

Authors

Pan, Y.,Weng, J.,Kabaleeswaran, V.,Li, H.,Cao, Y.,Bhosle, R.C.,Zhou, M. (deposition date: 2008-08-26, release date: 2008-09-23, Last modification date: 2023-08-30)

Primary citation

Pan, Y.,Weng, J.,Kabaleeswaran, V.,Li, H.,Cao, Y.,Bhosle, R.C.,Zhou, M.
Cortisone dissociates the Shaker family K+ channels from their beta subunits.
Nat.Chem.Biol., 4:708-714, 2008

PubMed Abstract: The Shaker family voltage-dependent potassium channels (Kv1) are expressed in a wide variety of cells and are essential for cellular excitability. In humans, loss-of-function mutations of Kv1 channels lead to hyperexcitability and are directly linked to episodic ataxia and atrial fibrillation. All Kv1 channels assemble with beta subunits (Kv betas), and certain Kv betas, for example Kv beta 1, have an N-terminal segment that closes the channel by the N-type inactivation mechanism. In principle, dissociation of Kv beta 1, although never reported, should eliminate inactivation and thus potentiate Kv1 current. We found that cortisone increases rat Kv1 channel activity by binding to Kv beta 1. A crystal structure of the Kv beta-cortisone complex was solved to 1.82-A resolution and revealed novel cortisone binding sites. Further studies demonstrated that cortisone promotes dissociation of Kv beta. The new mode of channel modulation may be explored by native or synthetic ligands to fine-tune cellular excitability.

PubMed: 18806782
DOI: 10.1038/nchembio.114

Experimental method

X-RAY DIFFRACTION (2 Å)