title: Solution structure of the cyclic-nucleotide binding homology domain of a KCNH channel.
abstract: The carboxy-terminal region of the KCNH family of potassium channels contains a cyclic-nucleotide binding homology domain (CNBHD) that is important for channel gating and trafficking. The solution structure of the CNBHD of the KCNH potassium of zebrafish was determined using solution NMR spectroscopy. This domain exists as a monomer under solution conditions and adopts a similar fold to that determined by X-ray crystallography. The CNBHD does not bind cAMP because residue Y740 blocks the entry of cyclic-nucleotide to the binding pocket. Relaxation results show that the CNBHD is rigid except that some residues in the loop between β6 and β7 are flexible. Our results will be useful to understand the gating mechanism of KCNH family members through the CNBHD.
authors.affiliation: Institute of Chemical & Engineering Sciences, Agency for Science, Technology and Research (A∗STAR), Singapore 627833, Singapore.
authors.forename: Qingxin
authors.initials: Q
authors.lastname: Li
authors.affiliation: Experimental Therapeutics Centre, Agency for Science, Technology and Research (A∗STAR), Singapore 138669, Singapore.
authors.forename: Hui Qi
authors.initials: HQ
authors.lastname: Ng
authors.affiliation: Division of Structural Biology and Biochemistry, School of Biological Sciences, Nanyang Technological University, 60 Nanyang Drive, Singapore 637511, Singapore.
authors.forename: Ho Sup
authors.initials: HS
authors.lastname: Yoon
authors.affiliation: Experimental Therapeutics Centre, Agency for Science, Technology and Research (A∗STAR), Singapore 138669, Singapore. Electronic address: cbkang@etc.a-star.edu.sg.
authors.forename: Congbao
authors.initials: C
authors.lastname: Kang
mesh_terms: D000818:Animals; D001665:Binding Sites; D000242:Cyclic AMP / Q000737:chemistry; D008958:Models, Molecular; D019906:Nuclear Magnetic Resonance, Biomolecular; D024642:Potassium Channels, Voltage-Gated / Q000737:chemistry*; D011485:Protein Binding; D017433:Protein Structure, Secondary; D012996:Solutions; D015027:Zebrafish; D029961:Zebrafish Proteins / Q000737:chemistry*
chemical_list: C000593379:KCNH3 protein, zebrafish; D024642:Potassium Channels, Voltage-Gated; D012996:Solutions; D029961:Zebrafish Proteins; D000242:Cyclic AMP
keywords: Cyclic-nucleotide binding domain; KCNH channel; NMR; Protein structure; Voltage-gated potassium channel