Biomaterial Database

Steric hindrance between S4 and S5 of the KCNQ1/KCNE1 channel hampers pore opening. 2014

Koichi Nakajo, and Yoshihiro Kubo

1] Division of Biophysics and Neurobiology, National Institute for Physiological Sciences, Okazaki, Aichi 444-8585, Japan [2] Department of Physiological Sciences, Hayama, Kanagawa 240-0193, Japan.

In voltage-gated K(+) channels, membrane depolarization induces an upward movement of the voltage-sensing domains (VSD) that triggers pore opening. KCNQ1 is a voltage-gated K(+) channel and its gating behaviour is substantially modulated by auxiliary subunit KCNE proteins. KCNE1, for example, markedly shifts the voltage dependence of KCNQ1 towards the positive direction and slows down the activation kinetics. Here we identify two phenylalanine residues on KCNQ1, Phe232 on S4 (VSD) and Phe279 on S5 (pore domain) to be responsible for the gating modulation by KCNE1. Phe232 collides with Phe279 during the course of the VSD movement and hinders KCNQ1 channel from opening in the presence of KCNE1. This steric hindrance caused by the bulky amino-acid residues destabilizes the open state and thus shifts the voltage dependence of KCNQ1/KCNE1 channel.

UI	MeSH Term	Description	Entries
D008958	Models, Molecular	Models used experimentally or theoretically to study molecular shape, electronic properties, or interactions; includes analogous molecules, computer-generated graphics, and mechanical structures.	Molecular Models,Model, Molecular,Molecular Model
D010649	Phenylalanine	An essential aromatic amino acid that is a precursor of MELANIN; DOPAMINE; noradrenalin (NOREPINEPHRINE), and THYROXINE.	Endorphenyl,L-Phenylalanine,Phenylalanine, L-Isomer,L-Isomer Phenylalanine,Phenylalanine, L Isomer
D002462	Cell Membrane	The lipid- and protein-containing, selectively permeable membrane that surrounds the cytoplasm in prokaryotic and eukaryotic cells.	Plasma Membrane,Cytoplasmic Membrane,Cell Membranes,Cytoplasmic Membranes,Membrane, Cell,Membrane, Cytoplasmic,Membrane, Plasma,Membranes, Cell,Membranes, Cytoplasmic,Membranes, Plasma,Plasma Membranes
D006801	Humans	Members of the species Homo sapiens.	Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D051657	KCNQ1 Potassium Channel	A voltage-gated potassium channel that is expressed primarily in the HEART.	KCNQ1 Protein,KVLQT1 Protein,Kv7.1 Potassium Channel,Voltage-Gated K+ Channel KCNQ1,Potassium Channel, KCNQ1,Potassium Channel, Kv7.1,Voltage Gated K+ Channel KCNQ1
D020816	Amino Acid Motifs	Three-dimensional protein structural elements that are composed of a combination of secondary structures. They include HELIX-LOOP-HELIX MOTIFS and ZINC FINGERS. Motifs are typically the most conserved regions of PROTEIN DOMAINS and are critical for domain function. However, the same motif may occur in proteins or enzymes with different functions.	AA Motifs,Motifs, Amino Acid,Protein Motifs,Protein Structure, Supersecondary,Supersecondary Protein Structure,AA Motif,Amino Acid Motif,Motif, AA,Motif, Amino Acid,Motif, Protein,Motifs, AA,Motifs, Protein,Protein Motif,Protein Structures, Supersecondary,Supersecondary Protein Structures
D024642	Potassium Channels, Voltage-Gated	Potassium channel whose permeability to ions is extremely sensitive to the transmembrane potential difference. The opening of these channels is induced by the membrane depolarization of the ACTION POTENTIAL.	Voltage-Gated Potassium Channels,Kv Potassium Channels,Potassium Channel, Voltage-Gated,Voltage-Gated K+ Channels,Voltage-Gated Potassium Channel,K+ Channels, Voltage-Gated,Potassium Channel, Voltage Gated,Potassium Channels, Kv,Potassium Channels, Voltage Gated,Voltage Gated K+ Channels,Voltage Gated Potassium Channel,Voltage Gated Potassium Channels