title: The single transmembrane segment determines the modulatory function of the BK channel auxiliary γ subunit.
abstract: The large-conductance, calcium-activated potassium (BK) channels consist of the pore-forming, voltage- and Ca(2+)-sensing α subunits (BKα) and the tissue-specific auxiliary β and γ subunits. The BK channel γ1 subunit is a leucine-rich repeat (LRR)-containing membrane protein that potently facilitates BK channel activation in many tissues and cell types through a vast shift in the voltage dependence of channel activation by ∼140 mV in the hyperpolarizing direction. In this study, we found that the single transmembrane (TM) segment together with its flanking charged residues is sufficient to fully modulate BK channels upon its transplantation into the structurally unrelated β1 subunit. We identified Phe273 and its neighboring residues in the middle of the TM segment and a minimum of three intracellular juxtamembrane Arg residues as important for the γ1 subunit's modulatory function and observed functional coupling between residues of these two locations. We concluded that the TM segment is a key molecular determinant for channel association and modulation and that the intracellular positively charged cluster is involved mainly in channel association, likely through its TM-anchoring effect. Our findings provide insights into the structure-function relationship of the γ1 subunit in understanding its potent modulatory effects on BK channels.
authors.affiliation: Department of Anesthesiology and Perioperative Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX 77030.
authors.forename: Qin
authors.initials: Q
authors.lastname: Li
authors.affiliation: Department of Anesthesiology and Perioperative Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX 77030.
authors.forename: Xin
authors.initials: X
authors.lastname: Guan
authors.affiliation: Department of Anesthesiology and Perioperative Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX 77030.
authors.forename: Karen
authors.initials: K
authors.lastname: Yen
authors.affiliation: Department of Anesthesiology and Perioperative Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX 77030.
authors.forename: Jiyuan
authors.initials: J
authors.lastname: Zhang
authors.affiliation: Department of Anesthesiology and Perioperative Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX 77030 jyan1@mdanderson.org.
authors.forename: Jiusheng
authors.initials: J
authors.lastname: Yan
mesh_terms: D000200:Action Potentials; D001120:Arginine / Q000737:chemistry / Q000378:metabolism; D057809:HEK293 Cells; D006801:Humans; D015640:Ion Channel Gating; D051036:Large-Conductance Calcium-Activated Potassium Channels / Q000737:chemistry / Q000378:metabolism*; D000072417:Protein Domains; D021122:Protein Subunits / Q000737:chemistry / Q000378:metabolism
chemical_list: D051036:Large-Conductance Calcium-Activated Potassium Channels; D021122:Protein Subunits; D001120:Arginine