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XB-ART-57192
Elife January 1, 2020; 9
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Aromatic interactions with membrane modulate human BK channel activation.

Yazdani M , Zhang G , Jia Z , Shi J , Cui J , Chen J .


Abstract
Large-conductance potassium (BK) channels are transmembrane (TM) proteins that can be synergistically and independently activated by membrane voltage and intracellular Ca2+. The only covalent connection between the cytosolic Ca2+ sensing domain and the TM pore and voltage sensing domains is a 15-residue ''C-linker''. To determine the linker''s role in human BK activation, we designed a series of linker sequence scrambling mutants to suppress potential complex interplay of specific interactions with the rest of the protein. The results revealed a surprising sensitivity of BK activation to the linker sequence. Combining atomistic simulations and further mutagenesis experiments, we demonstrated that nonspecific interactions of the linker with membrane alone could directly modulate BK activation. The C-linker thus plays more direct roles in mediating allosteric coupling between BK domains than previously assumed. Our results suggest that covalent linkers could directly modulate TM protein function and should be considered an integral component of the sensing apparatus.

PubMed ID: 32597752
PMC ID: PMC7371421
Article link: Elife
Grant support: [+]

Species referenced: Xenopus laevis
Genes referenced: pgd tbl1x ttn
GO keywords: large conductance calcium-activated potassium channel activity


Article Images: [+] show captions
References [+] :
Bavro, Structure of a KirBac potassium channel with an open bundle crossing indicates a mechanism of channel gating. 2012, Pubmed