Semisynthetic K~+ channels show that the constricted conformation of the selectivity filter is not the C-type inactivated state

Devaraneni P.K.; Komarov A.G.; Costantino C.A.Devereaux J.J.Matulef K.Valiyaveetil F.I.

首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >Semisynthetic K~+ channels show that the constricted conformation of the selectivity filter is not the C-type inactivated state

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Semisynthetic K~+ channels show that the constricted conformation of the selectivity filter is not the C-type inactivated state

机译：Semisynthetic K~+ channels show that the constricted conformation of the selectivity filter is not the C-type inactivated state

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摘要

C-type inactivation of K~+ channels plays a key role in modulating cellular excitability. During C-type inactivation, the selectivity filter of a K~+ channel changes conformation from a conductive to a nonconductive state. Crystal structures of the KcsA channel determined at low K~+ or in the open state revealed a constricted conformation of the selectivity filter, which was proposed to represent the C-type inactivated state. However, structural studies on other K~+ channels do not support the constricted conformation as the C-type inactivated state. In this study, we address whether the constricted conformation of the selectivity filter is in fact the C-type inactivated state. The constricted conformation can be blocked by substituting the first conserved glycine in the selectivity filter with the unnatural amino acid D-Alanine. Protein semisynthesis was used to introduce D-Alanine into the selectivity filters of the KcsA channel and the voltage-gated K~+ channel K_vAP. For semisynthesis of the K_vAP channel, we developed a modular approach in which chemical synthesis is limited to the selectivity filter whereas the rest of the protein is obtained by recombinant means. Using the semisynthetic KcsA and KvAP channels, we show that blocking the constricted conformation of the selectivity filter does not prevent inactivation, which suggests that the constricted conformation is not the C-type inactivated state.

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《Proceedings of the National Academy of Sciences of the United States of America》 |2013年第39期|15698-15703|共6页
作者
Devaraneni P.K.; Komarov A.G.; Costantino C.A.Devereaux J.J.Matulef K.Valiyaveetil F.I.;
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作者单位

Program in Chemical Biology, Department of Physiology and Pharmacology, Oregon Health and Science University, Portland, OR 97239, United States;

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收录信息美国《科学引文索引》(SCI);美国《生物学医学文摘》(MEDLINE);美国《化学文摘》(CA);
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正文语种英语
中图分类自然科学总论;
关键词
channels; conformation; type;

Semisynthetic K~+ channels show that the constricted conformation of the selectivity filter is not the C-type inactivated state

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