Mg2+ and Ca2+ Differentially Regulate DNA Binding and Dimerization of DREAM

Osawa, Masatoshi; Dace, Alexandra; Tong, Kit I.; Valiveti, Aswani; Ikura, Mitsuhiko; Ames, James B.

doi:10.1074/jbc.m500338200

Cited by 106 publications

(177 citation statements)

References 42 publications

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“…Even an EF3,EF4 fragment (amino acid 161 – 256) of KChIP3 showed a reduced spectral resolution in the absence of Ca 2+ , corroborating the central role of EF3 and EF4 in Ca 2+ binding and associated conformational changes [40]. KChIPs may also form oligomers in a divalent cation-dependent manner, with Ca 2+ binding to EF3 and EF4 favoring dimer formation [33,39,41]. KChIP3 has even been reported to oligomerize with calcineurin and calmodulin [42].…”

Section: Ca2+ Binding Properties and Associated Conformational Changementioning

confidence: 87%

“…The experimental results showed that KChIPs are able to bind both Ca 2+ and Mg 2+ via their EF-hands, and that they exhibit high and low affinity Ca 2+ binding (Figure 2) [1,34–39]. K d values for high affinity Ca 2+ binding range between 10 and 50 μM, and for low affinity Ca 2+ binding between 2 and 3 mM [35,37,38].…”

Section: Ca2+ Binding Properties and Associated Conformational Changementioning

confidence: 99%

“…High affinity Ca 2+ binding is distorted with ΔEF3 or ΔEF4, but not with ΔEF2, which leads to a drop in Mg 2+ affinity [34,35,37]. Three Ca 2+ ions may bind, with descending affinity, to EF3, EF4 and EF2, however, in the presence of Mg 2+ both wild-type and ΔEF2 KChIPs have been shown to bind only two Ca 2+ ions [39]. Taken together, these findings suggest that in KChIPs EF2 mediates low affinity Ca 2+ binding and is occupied by Mg 2+ under physiological conditions, whereas EF3 and EF4 mediate high affinity Ca 2+ binding [34–37,39].…”

Section: Ca2+ Binding Properties and Associated Conformational Changementioning

confidence: 99%

“…Three Ca 2+ ions may bind, with descending affinity, to EF3, EF4 and EF2, however, in the presence of Mg 2+ both wild-type and ΔEF2 KChIPs have been shown to bind only two Ca 2+ ions [39]. Taken together, these findings suggest that in KChIPs EF2 mediates low affinity Ca 2+ binding and is occupied by Mg 2+ under physiological conditions, whereas EF3 and EF4 mediate high affinity Ca 2+ binding [34–37,39]. The data are in accordance with crystal structure and NMR analysis, which showed only two bound Ca 2+ ions per KChIP subunit residing in EF3 and EF4 (Figure 2) [30–33].…”

Section: Ca2+ Binding Properties and Associated Conformational Changementioning

confidence: 99%

“…Ca 2+ withdrawal from KChIP1 [30], KChIP2 [38] and KChIP3 [39] has been shown to cause a reduced helical content and increased flexibility of these proteins. Even an EF3,EF4 fragment (amino acid 161 – 256) of KChIP3 showed a reduced spectral resolution in the absence of Ca 2+ , corroborating the central role of EF3 and EF4 in Ca 2+ binding and associated conformational changes [40].…”

Section: Ca2+ Binding Properties and Associated Conformational Changementioning

confidence: 99%

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Kv channel-interacting proteins as neuronal and non-neuronal calcium sensors

Bähring

2018

Channels

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Kv channel-interacting proteins (KChIPs) belong to the neuronal calcium sensor (NCS) family of Ca2+-binding EF-hand proteins. KChIPs constitute a group of specific auxiliary β-subunits for Kv4 channels, the molecular substrate of transient potassium currents in both neuronal and non-neuronal tissues. Moreover, KChIPs can interact with presenilins to control ER calcium signaling and apoptosis, and with DNA to control gene transcription. Ca2+ binding via their EF-hands, with the consequence of conformational changes, is well documented for KChIPs. Moreover, the Ca2+ dependence of the presenilin/KChIP complex may be related to Alzheimer’s disease and the Ca2+ dependence of the DNA/KChIP complex to pain sensing. However, only in few cases could the Ca2+ binding to KChIPs be directly linked to the control of excitability in nerve and muscle cells known to express Kv4/KChIP channel complexes. This review summarizes current knowledge about the Ca2+ binding properties of KChIPs and the Ca2+ dependencies of macromolecular complexes containing KChIPs, including those with presenilins, DNA and especially Kv4 channels. The respective physiological or pathophysiolgical roles of Ca2+ binding to KChIPs are discussed.

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Section: Ca2+ Binding Properties and Associated Conformational Changementioning

confidence: 87%

Section: Ca2+ Binding Properties and Associated Conformational Changementioning

confidence: 99%

Section: Ca2+ Binding Properties and Associated Conformational Changementioning

confidence: 99%

Section: Ca2+ Binding Properties and Associated Conformational Changementioning

confidence: 99%

Section: Ca2+ Binding Properties and Associated Conformational Changementioning

confidence: 99%

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Kv channel-interacting proteins as neuronal and non-neuronal calcium sensors

Bähring

2018

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Molecular insight of DREAM and presenilin 1 C‐terminal fragment interactions

Pham

Mikšovská

2016

FEBS Letters

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Edited by Alfonso ValenciaInteractions between downstream regulatory element antagonist modulator (DREAM) and presenilin 1 (PS1) are related to numerous neuronal processes. We demonstrate that association of PS1 carboxyl peptide (residues 445-467, HL9) with DREAM is calcium dependent and stabilized by a cluster of three aromatic residues: F462 and F465 from PS1 and F252 from DREAM. Additional stabilization is provided by residues in a loop connecting a helices 7 and 8 in DREAM and residues of PS1, namely cation-p interactions between R200 in DREAM and F465 in PS1 and the salt bridges formed by R207 in DREAM and D450 and D458 in PS1.

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