6y7q
From Proteopedia
Crystal Structure of the N-terminal PAS domain from the hERG3 Potassium Channel
Structural highlights
FunctionKCNH7_HUMAN Pore-forming (alpha) subunit of voltage-gated potassium channel. Channel properties may be modulated by cAMP and subunit assembly. Publication Abstract from PubMedThe ether-a-go-go (EAG) family of voltage gated K+ channels are important regulators of neuronal and cardiac action potential firing (excitability) and have major roles in human diseases such as epilepsy, schizophrenia, cancer and sudden cardiac death. A defining feature of EAG (Kv10-12) channels is a highly conserved domain on the amino-terminus, known as the eag-domain, consisting of a PAS domain capped by a short sequence containing an amphipathic helix (Cap-domain). The PAS and Cap domains are both vital for the normal function of EAG channels. Using heme-affinity pull-down assays and proteomics of lysates from primary cortical neurons, we identified that an EAG channel, hERG3 (Kv11.3), binds to heme. In whole cell electrophysiology experiments, we identified that heme inhibits hERG3 channel activity. In addition, we expressed the Cap and PAS domain of hERG3 in E.coli and, using spectroscopy and kinetics, identified the PAS domain as the location for heme binding. The results identify heme as a regulator of hERG3 channel activity. These observations are discussed in the context of the emerging role for heme as a regulator of ion channel activity in cells. Discovery of a heme-binding domain in a neuronal voltage-gated potassium channel.,Burton MJ, Cresser-Brown J, Thomas M, Portolano N, Basran J, Freeman SL, Kwon H, Bottrill AR, Llansola-Portoles MJ, Pascal AA, Jukes-Jones R, Chernova T, Schmid R, Davies NW, Storey NM, Dorlet P, Moody PCE, Mitcheson JS, Raven EL J Biol Chem. 2020 Jul 28. pii: RA120.014150. doi: 10.1074/jbc.RA120.014150. PMID:32723862[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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