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BK channels: multiple sensors, one activation gate.

Yang H, Zhang G, Cui J - Front Physiol (2015)

Bottom Line: To achieve spatially and temporally regulated ion flux in cells, many ion channels have evolved sensors to detect various environmental stimuli or the metabolic states of the cell and trigger global conformational changes, thereby dynamically operate the opening and closing of their activation gate.With the rapidly growing structural and functional information of different types of ion channels, it is now critical to understand how ion channel sensors dynamically control their gates at molecular and atomic level.The voltage and Ca(2+) activated BK channels, a K(+) channel with an electrical sensor and multiple chemical sensors, provide a unique model system for us to understand how physical and chemical energy synergistically operate its activation gate.

View Article: PubMed Central - PubMed

Affiliation: Ion Channel Research Unit, Duke University Medical Center Durham, NC, USA ; Department of Biochemistry, Duke University Medical Center Durham, NC, USA.

ABSTRACT
Ion transport across cell membranes is essential to cell communication and signaling. Passive ion transport is mediated by ion channels, membrane proteins that create ion conducting pores across cell membrane to allow ion flux down electrochemical gradient. Under physiological conditions, majority of ion channel pores are not constitutively open. Instead, structural region(s) within these pores breaks the continuity of the aqueous ion pathway, thereby serves as activation gate(s) to control ions flow in and out. To achieve spatially and temporally regulated ion flux in cells, many ion channels have evolved sensors to detect various environmental stimuli or the metabolic states of the cell and trigger global conformational changes, thereby dynamically operate the opening and closing of their activation gate. The sensors of ion channels can be broadly categorized as chemical sensors and physical sensors to respond to chemical (such as neural transmitters, nucleotides and ions) and physical (such as voltage, mechanical force and temperature) signals, respectively. With the rapidly growing structural and functional information of different types of ion channels, it is now critical to understand how ion channel sensors dynamically control their gates at molecular and atomic level. The voltage and Ca(2+) activated BK channels, a K(+) channel with an electrical sensor and multiple chemical sensors, provide a unique model system for us to understand how physical and chemical energy synergistically operate its activation gate.

No MeSH data available.


Related in: MedlinePlus

Assembly of the BK channel structural domains. (A) Sequence alignment of the inner helices and the C-linkers of different K+ channels. Residues that can increase peptide flexibility and alter α helix orientation (i.e., Glycine and Proline) are highlighted in yellow. (B) The C-termini of inner helix and the C-linkers of different K+ channels may point to different directions. The PGDs of MthK (PDB ID: 1LNQ), Kv1.2 (PDB ID: 2R9R) and GsuK (PDB ID: 4GX5) channels are superimposed at the selectivity filter by using UCSF Chimera. (C) The relative assembly of the VSD and the CTD in BK channels might be different from the homology model shown in Figure 1B with a relative ~90° angular rotation about the central axis between the PGD and CTD.
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Figure 4: Assembly of the BK channel structural domains. (A) Sequence alignment of the inner helices and the C-linkers of different K+ channels. Residues that can increase peptide flexibility and alter α helix orientation (i.e., Glycine and Proline) are highlighted in yellow. (B) The C-termini of inner helix and the C-linkers of different K+ channels may point to different directions. The PGDs of MthK (PDB ID: 1LNQ), Kv1.2 (PDB ID: 2R9R) and GsuK (PDB ID: 4GX5) channels are superimposed at the selectivity filter by using UCSF Chimera. (C) The relative assembly of the VSD and the CTD in BK channels might be different from the homology model shown in Figure 1B with a relative ~90° angular rotation about the central axis between the PGD and CTD.

Mentions: Third, the orientation of the pore-lining residues in BK channels is different from those of Kv channels. Cysteine substitution and modification studies of the BK S6 demonstrated that A313, A316, and S317 are facing to the inner pore, while the corresponding residues in Shaker K+ channels tend to face away from the aqueous environment (Zhou et al., 2011). Therefore, a relative rotation of the S6 has to occur to account for this experimental observation. One possible cause of this rotation may derive from the two consecutive glycine residues (G310 and G311) in BK channel S6 (Figure 4A). An additional glycine residue (G310) may make S6 more flexible around the highly conserved “Glycine hinge” region in Kv channels, thereby rearranging the orientations of the residues downstream of this di-glycine hinge.


BK channels: multiple sensors, one activation gate.

Yang H, Zhang G, Cui J - Front Physiol (2015)

Assembly of the BK channel structural domains. (A) Sequence alignment of the inner helices and the C-linkers of different K+ channels. Residues that can increase peptide flexibility and alter α helix orientation (i.e., Glycine and Proline) are highlighted in yellow. (B) The C-termini of inner helix and the C-linkers of different K+ channels may point to different directions. The PGDs of MthK (PDB ID: 1LNQ), Kv1.2 (PDB ID: 2R9R) and GsuK (PDB ID: 4GX5) channels are superimposed at the selectivity filter by using UCSF Chimera. (C) The relative assembly of the VSD and the CTD in BK channels might be different from the homology model shown in Figure 1B with a relative ~90° angular rotation about the central axis between the PGD and CTD.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4319557&req=5

Figure 4: Assembly of the BK channel structural domains. (A) Sequence alignment of the inner helices and the C-linkers of different K+ channels. Residues that can increase peptide flexibility and alter α helix orientation (i.e., Glycine and Proline) are highlighted in yellow. (B) The C-termini of inner helix and the C-linkers of different K+ channels may point to different directions. The PGDs of MthK (PDB ID: 1LNQ), Kv1.2 (PDB ID: 2R9R) and GsuK (PDB ID: 4GX5) channels are superimposed at the selectivity filter by using UCSF Chimera. (C) The relative assembly of the VSD and the CTD in BK channels might be different from the homology model shown in Figure 1B with a relative ~90° angular rotation about the central axis between the PGD and CTD.
Mentions: Third, the orientation of the pore-lining residues in BK channels is different from those of Kv channels. Cysteine substitution and modification studies of the BK S6 demonstrated that A313, A316, and S317 are facing to the inner pore, while the corresponding residues in Shaker K+ channels tend to face away from the aqueous environment (Zhou et al., 2011). Therefore, a relative rotation of the S6 has to occur to account for this experimental observation. One possible cause of this rotation may derive from the two consecutive glycine residues (G310 and G311) in BK channel S6 (Figure 4A). An additional glycine residue (G310) may make S6 more flexible around the highly conserved “Glycine hinge” region in Kv channels, thereby rearranging the orientations of the residues downstream of this di-glycine hinge.

Bottom Line: To achieve spatially and temporally regulated ion flux in cells, many ion channels have evolved sensors to detect various environmental stimuli or the metabolic states of the cell and trigger global conformational changes, thereby dynamically operate the opening and closing of their activation gate.With the rapidly growing structural and functional information of different types of ion channels, it is now critical to understand how ion channel sensors dynamically control their gates at molecular and atomic level.The voltage and Ca(2+) activated BK channels, a K(+) channel with an electrical sensor and multiple chemical sensors, provide a unique model system for us to understand how physical and chemical energy synergistically operate its activation gate.

View Article: PubMed Central - PubMed

Affiliation: Ion Channel Research Unit, Duke University Medical Center Durham, NC, USA ; Department of Biochemistry, Duke University Medical Center Durham, NC, USA.

ABSTRACT
Ion transport across cell membranes is essential to cell communication and signaling. Passive ion transport is mediated by ion channels, membrane proteins that create ion conducting pores across cell membrane to allow ion flux down electrochemical gradient. Under physiological conditions, majority of ion channel pores are not constitutively open. Instead, structural region(s) within these pores breaks the continuity of the aqueous ion pathway, thereby serves as activation gate(s) to control ions flow in and out. To achieve spatially and temporally regulated ion flux in cells, many ion channels have evolved sensors to detect various environmental stimuli or the metabolic states of the cell and trigger global conformational changes, thereby dynamically operate the opening and closing of their activation gate. The sensors of ion channels can be broadly categorized as chemical sensors and physical sensors to respond to chemical (such as neural transmitters, nucleotides and ions) and physical (such as voltage, mechanical force and temperature) signals, respectively. With the rapidly growing structural and functional information of different types of ion channels, it is now critical to understand how ion channel sensors dynamically control their gates at molecular and atomic level. The voltage and Ca(2+) activated BK channels, a K(+) channel with an electrical sensor and multiple chemical sensors, provide a unique model system for us to understand how physical and chemical energy synergistically operate its activation gate.

No MeSH data available.


Related in: MedlinePlus