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The RCK2 domain of the human BKCa channel is a calcium sensor

Yusifov, Taleh and Savalli, Nicoletta and Gandhi, Chris S. and Ottolia, Michela and Olcese, Riccardo (2008) The RCK2 domain of the human BKCa channel is a calcium sensor. Proceedings of the National Academy of Sciences of the United States of America, 105 (1). pp. 376-381. ISSN 0027-8424. http://resolver.caltech.edu/CaltechAUTHORS:YUSpnas08

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Abstract

Large conductance voltage and Ca2+-dependent K+ channels (BKCa) are activated by both membrane depolarization and intracellular Ca2+. Recent studies on bacterial channels have proposed that a Ca2+-induced conformational change within specialized regulators of K+ conductance (RCK) domains is responsible for channel gating. Each pore-forming α subunit of the homotetrameric BKCa channel is expected to contain two intracellular RCK domains. The first RCK domain in BKCa channels (RCK1) has been shown to contain residues critical for Ca2+ sensitivity, possibly participating in the formation of a Ca2+-binding site. The location and structure of the second RCK domain in the BKCa channel (RCK2) is still being examined, and the presence of a high-affinity Ca2+-binding site within this region is not yet established. Here, we present a structure-based alignment of the C terminus of BKCa and prokaryotic RCK domains that reveal the location of a second RCK domain in human BKCa channels (hSloRCK2). hSloRCK2 includes a high-affinity Ca2+-binding site (Ca bowl) and contains similar secondary structural elements as the bacterial RCK domains. Using CD spectroscopy, we provide evidence that hSloRCK2 undergoes a Ca2+-induced change in conformation, associated with an α-to-β structural transition. We also show that the Ca bowl is an essential element for the Ca2+-induced rearrangement of hSloRCK2. We speculate that the molecular rearrangements of RCK2 likely underlie the Ca2+-dependent gating mechanism of BKCa channels. A structural model of the heterodimeric complex of hSloRCK1 and hSloRCK2 domains is discussed.


Item Type:Article
Related URLs:
URLURL TypeDescription
http://dx.doi.org/10.1073/pnas.0705261105DOIUNSPECIFIED
http://www.pnas.org/content/105/1/376PublisherUNSPECIFIED
Additional Information:© 2008 by the National Academy of Sciences. Edited by Ramón Latorre, Centro de Estudios Cientifícos, Valdivia, Chile, and approved November 15, 2007 (received for review June 7, 2007). Published online before print December 27, 2007, doi: 10.1073/pnas.0705261105. This article is a PNAS Direct Submission. We thank Ligia Toro (University of California, Los Angeles) for the hSlo clone and the members of the R.O. and D. Rees laboratories for constructive discussions. This work was supported by National Institutes of Health/National Institute of Neurological Disorders and Stroke Research Grant RO1NS043240 (to R.O.). Author contributions: T.Y., N.S., C.S.G., M.O., and R.O. designed research, performed research, analyzed data, and wrote the paper. The authors declare no conflict of interest. This article contains supporting information online at www.pnas.org/cgi/content/full/0705261105/DC1.
Funders:
Funding AgencyGrant Number
National Institute of Neurological Disorders and StrokeRO1NS043240
Subject Keywords:BK channel; circular dichroism; MaxiK; RCK; structural modeling
Issue or Number:1
Record Number:CaltechAUTHORS:YUSpnas08
Persistent URL:http://resolver.caltech.edu/CaltechAUTHORS:YUSpnas08
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:12121
Collection:CaltechAUTHORS
Deposited By: Tony Diaz
Deposited On:01 Nov 2008 01:50
Last Modified:09 Nov 2017 23:56

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