Critical role of conserved proline residues in the transmembrane segment 4 voltage sensor function and in the gating of L-type calcium channels

作者: H. Yamaguchi , J. N. Muth , M. Varadi , A. Schwartz , G. Varadi

DOI: 10.1073/PNAS.96.4.1357

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摘要: Abstract The fourth transmembrane segment (S4) has been shown to function as a voltage sensor in voltage-gated channels. On membrane depolarization, stretch of S4 moves outward and initiates number conformational changes that ultimately lead channel opening. Conserved proline residues are the middle motifs I III voltage-dependent Ca2+ Because often introduces “kink” into helical structure proteins, these might have an intrinsic sensor. Here, we report removal prolines results dramatic shortening open time whereas introduction extra corresponding positions motif IIS4 IVS4 lengthens time. The S4s with residue showed clear positive correlation mean channel. was >11-fold longer for mutagenized all four compared had no region. Additionally, slowed activation kinetics shifted dependence inactivation hyperpolarized direction. Our strongly suggest critical stabilizing state Moreover, it is suggested IS4 IIIS4 contribute opening more efficiently than IVS4.

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