NDLI: The single transmembrane segment determines the modulatory function of the BK channel auxiliary γ subunit

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The single transmembrane segment determines the modulatory function of the BK channel auxiliary γ subunit

Content Provider	Scilit
Author	Li, Qin Guan, Xin Yen, Karen Zhang, Jiyuan Yan, Jiusheng
Copyright Year	2016
Description	Journal: The Journal of general physiology 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.
Related Links	https://rupress.org/jgp/article-pdf/147/4/337/578898/jgp_201511551.pdf https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4810070/pdf http://jgp.rupress.org/content/147/4/337.full.pdf
ISSN	00221295
DOI	10.1085/jgp.201511551
Journal	The Journal of general physiology
Issue Number	4
Volume Number	147
Language	English
Publisher	Rockefeller University Press
Publisher Date	2016-03-28
Access Restriction	Open
Subject Keyword	Journal: The Journal of general physiology Biochemistry and Molecular Biology Modulatory Function Bk Channel Structurally
Content Type	Text
Resource Type	Article
Subject	Physiology

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