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CALM binds KCNQ1. 73 / 74
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"Thus, the interaction of calmodulin and Kv7.1 appears to be critical for expression and function of I Ks , with the intriguing possibility that regulatory mechanisms could also involve some form of CaMKII interaction with calmodulin and Kv7.1 or KCNE1."
24600393
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"Helix A (residues 370–386) and helix B (residues 504–531) mediate binding of KCNQ1 with CaM, which is required for normal KCNQ1 channel gating, folding and membrane trafficking [9–11] ."
24713462
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"CaM binds to the proximal C-terminus of KCNQ1 and is thought to compete with PIP 2 to stabilize the KCNQ1 open state; this also occurs in physiological relevant complexes in which KCNQ1-CaM co-assembles with the KCNE1 ancillary subunit to form I Ks complexes (see below) ( xref )."
32655402
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"This disturbed calmodulin- Kv7.1 interaction may be important for channel expression."
24600393
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"Other studies found that CaM C-lobe bound to KCNQ1 does not coordinate Ca 2+ ions under 1 mM EGTA or 5 mM Ca 2+ conditions."
33310856
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"The three-dimensional cryo-EM structures of KCNQ1-CaM, KCNQ1/KCNE3-CaM and KCNQ2 channels have helped to explain some functional studies of KCNQ channels with or without different KCNE subunits."
33322401
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"Helix A (residues 370-386) and helix B (residues 504-531) mediate binding of KCNQ1 with CaM, which is required for normal KCNQ1 channel gating, folding and membrane trafficking [9-11]."
24713462
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"Cryo-EM Structure of a KCNQ1 and CaM Complex Reveals Insights into Congenital Long QT Syndrome."
28575668
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"One possibility is that Ca 2+ binding to KCNQ1 bound calmodulin exerts conformational effects that can be transmitted to co-assembled SMITs to Ca 2+ -dependently regulate myo-inositol intake."
28718502
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"To test whether CaM binding to KCNQ1 was dissociated by PIs, we fused each of the two C-terminal KCNQ1 CaM-binding regions (CBS1 and CBS2) to MBP and performed competition assays."
17317623
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"In this study, utilizing two VSD-PD coupling enhancers, namely, the membrane lipid phosphatidylinositol 4,5-bisphosphate (PIP 2 ) and a small-molecule ML277, we determined 2.5-3.5 Å resolution cryo-electron microscopy structures of full-length human KCNQ1-calmodulin (CaM) complex in the apo closed, ML277-bound open, and ML277-PIP 2 -bound open states."
36763058
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"According to the recent cryo-EM structure of KCNQ1-CaM, the lower S6 bends at the Pro-Ala-Gly motif."
33322401
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"On the other hand, helices A‐B in C‐terminal mediate the binding of KCNQ1 and CaM in charge of gating, folding, and membrane trafficking of the channel (Kinoshita et al., xref )."
31565860
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"Disruption of CaM interactions with Kv7.1 ( Ghosh et al., 2006; Shamgar et al., 2006 ), Kv7.2 ( Etxeberria et al., 2008 ), and the Kv7.2/Kv7.3 heteromer ( Liu and Devaux, 2014 ) by disease mutations h[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
29429937
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"Earlier reports of constitutive association of the Ca 2+ -binding protein calmodulin (CaM) with the C-terminus of KCNQ1 (Yus-Najera et al., xref ; Ghosh et al., xref ; Shamgar et al., xref ; Ciampa et al., xref ) prompted us to consider intracellular Ca 2+ as a putative ligand for KCNQ1-CaM complex."
22866036
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"Although no direct structure determination exists for KCNQ1-KCNE1 complexes, the structures of KCNQ1-CaM and KCNQ1-KCNE3-CaM have been solved and they also support the positioning of KCNEs in the aforementioned groove ( xref ) ( xref , xref )."
34247280
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"HF‐associated changes may also influence interaction of KCNQ1 with CaM, a calcium‐binding second messenger that is a regulator of I Ks inactivation gating and channel assembly. xref Specifically, CaM has been shown to interact with KCNQ1 via 2 CaM‐binding domains within helices A and B of the KCNQ1 carboxyl terminus in a process that is required for channel tetramerization. xref , xref Given the essential role of CaM in regulating I Ks , reduced expression of CaM, as has been consistently demonstrated in HF, may be involved in the pathologic regulation of I Ks in HF. xref , xref "
32865116
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"The recent cryo-EM structure of the KCNQ1 and CaM complex [XREF_BIBR] supported the idea that in the absence of PIP 2, the voltage sensor still moves but the pore remains closed."
33322401
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"Mutation in the CaM-binding motifs of KCNQ1 [29] is associated with LQTS."
26164367
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"Comparing the structures between KCNQ1-CaM and KCNQ1/KCNE3-CaM, Mackinnon et al. [ xref ] found that KCNE3 lies in between S1, S4, S5 and S6 from three different subunits, suggesting KCNE1 and KCNE3 might share a similar location when associated with KCNQ1."
33322401
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"To test whether CaM binding to KCNQ1 was dissociated by PIs, we fused each of the two C-terminal KCNQ1 CaM binding regions (CBS1 and CBS2) to MBP and performed competition assays."
17317623
sparser
"Recent biophysical studies and a cryo-EM structure of the KCNQ1-calmodulin complex have provided new insights into K V 7.1 channel function, and how interactions between KCNQ1 and KCNE subunits alter the gating properties of heteromultimeric channels."
35138621
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"Significantly, this arrangement is also displayed on the crystallographic complexes of CaM with Kv7.1 [ xref ], Kv7.4, Kv7.5 [ xref ] and a chimera between hA of Kv7.3 and hB of Kv7.2 [ xref ]."
30022004
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"Other mutations that affect PIP 2 or CaM binding to KCNQ1 underlie certain forms of the long QT syndrome and can result in sudden cardiac death ( Park et al., 2005; Ghosh et al., 2006; Shamgar et al.[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
17317623
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"Earlier reports of constitutive association of the Ca 2+ -binding protein calmodulin (CaM) with the C-terminus of KCNQ1 prompted us to consider intracellular Ca 2+ as a putative ligand for KCNQ1 and CaM complex."
22866036
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"These studies were motivated by the observed similarities between the suppression of KCNQ1 function by pharmacological disruption of KCNQ1-CaM interactions and the effects of KCNE4 co-expression on the channel."
21118809
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"The recently published cryo-EM structure of the KCNQ1 and CaM complex [12] falls within the conformational space of possible structures in the library."
30292722
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"In the presence of KCNE3 the architecture of human KCNQ1-CaM is similar to that of the Xenopus complex ( xref ) and thus we use the same nomenclature for secondary structure elements ( xref )."
31883792
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"Therefore, we considered the M520R mutation to affect the CaM-Kv7.1 interaction."
17482572
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"Thus, upon PIP2 depletion, calcium-bound CaM can bind to Kv7.1, mimic the PIP2 binding effect, and assist in channel activation ( xref )."
34149352
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"Together, these data support the idea that Apo/CaM:Kv7.4 interactions are essential for proper trafficking and are reminiscent of effects reported for mutations that disrupt the interaction between Ca[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
29429937
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"Together, the combined functional and simulation results suggest CaM interacts with the KCNQ1 S2-S3 linker during gating."
33310856
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"Here, we combine electrophysiology experiments and network analysis of molecular dynamics (MD) simulations to show that CaM interacts with the KCNQ1 VSD during voltage-dependent activation to modulate ionic current, despite PIP 2 presence in the membrane."
33310856
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"This study describes one physiological form of KCNQ1, depolarized voltage sensors with a closed pore in the absence of PIP 2, and reveals a regulatory interaction between CaM and KCNQ1 that may explain CaM mediated LQTS."
28575668
sparser
"In fact, when CaM does not interact with KCNQ1 due to mutations in the channel protein, it prevents tetramerization of KCNQ1, which is directly related with aberrant channel function and long QT syndrome."
31825788
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"Other studies found that CaM C-lobe bound to KCNQ1 does not coordinate Ca 2+ ions under 1 mM EGTA or 5 mM Ca 2+ conditions ( xref )."
33310856
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"CaM binding to Kv7.1 is also required for appropriate folding of the C-terminus and it is also necessary for correct channel trafficking to the plasma membrane [ xref , xref ]."
30022004
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"The results were close to identical to the analysis of the human KCNQ1 and CaM complex, reinforcing the findings from the human KCNQ1 and CaM simulations."
33310856
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"The overall RMSD between the human and Xenopus KCNQ1-CaM monomer is about 1.1 Å ( xref )."
31883792
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"Since structures of KCNQ1-CaM mentioned above were resolved at 0 mV, the voltage sensor of those channels was proposed to be in the activated conformation."
33322401
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"In this network, each node corresponded to an individual amino acid residue within the KCNQ1 and CaM complex."
33310856
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"Formation of functional tetramers requires CaM interaction with the KCNQ1 C-terminus."
16556866
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"A recent cryo-EM study showed that each Kv7.1 subunit associates with one calmodulin molecule [ xref ]."
29451064
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"Interestingly, co-immunoprecipitation experiments in yeast cells expressing wild-type Kv7.1 or mutated Kv7.1 with truncated α-helices showed that calmodulin can bind to the C-terminus of Kv7.1 ( xref )."
24600393
reach
"Other mutations that affect PIP 2 or CaM binding to KCNQ1 underlie certain forms of the long QT syndrome and can result in sudden cardiac death (Park et al., 2005; Ghosh et al., 2006; Shamgar et al., [MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
17317623
sparser
"Altogether, these data suggest that mutations located at this region could disrupt Kv7.1-calmodulin interactions resulting in defective trafficking."
33693037
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"Structurally, CaM binds the KCNQ1 C-terminal domain (CTD) such that CaM N-lobe associates with KCNQ1 HB and CaM C-lobe interacts with KCNQ1 HA ( xref ) ( xref , xref , xref , xref , xref )."
33310856
reach
"Recent biophysical studies and a cryo-EM structure of the KCNQ1-calmodulin complex have provided new insights into K V 7.1 channel function, and how interactions between KCNQ1 and KCNE subunits alter the gating properties of heteromultimeric channels."
35138621
sparser
"The recent cryo-EM structure of the KCNQ1-CaM complex [ xref ] supported the idea that in the absence of PIP 2 , the voltage sensor still moves but the pore remains closed."
33322401
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"Functionally, IKs is regulated by a number of interacting proteins and post‐translational modifications. xref – xref The IKs currents and the channel subunits KCNQ1 and KCNE1 proteins are regulated by the β‐adrenergic‐mediated protein kinase A– dependent phosphorylation, a process that might be pathogenic in heart failure. xref , xref – xref Likewise, IKs are calcium‐responsive currents, partly because of interaction of the KCNQ1 with calmodulin, which is a constitutive component of the K + channels. xref One might speculate that altered interactions of KCNQ1 and calmodulin, in the presence of KCNQ1 mutations, could perturb intracellular calcium homeostasis and affect the contractile performance of cardiac myocytes."
25616976
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"CaM binding to Kv7.1 is also required for appropriate folding of the C-terminus and it is also necessary for correct channel trafficking to the plasma membrane [47,48]."
30022004
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"First, the MD trajectories of the KCNQ1 and CaM complex were converted into a residue interaction network representation (XREF_FIG)."
33310856
sparser
"To test if the mutant M520R disrupts channel function by impairing the interaction of Kv7.1 with CaM, we performed yeast two-hybrid experiments ( Fig. 4 B)."
17482572
sparser
"This study describes one physiological form of KCNQ1, depolarized voltage sensors with a closed pore in the absence of PIP 2 , and reveals a regulatory interaction between CaM and KCNQ1 that may explain CaM-mediated LQTS."
28575668
sparser
"The interface between KCNE3 and KCNQ1-CaM consists of two parts: cytosolic interactions between KCNE3 and CaM ( xref ) and transmembrane interactions between KCNE3 and KCNQ1 ( xref )."
31883792
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"Indeed, structural comparison with the Apo/CaM:Kv7.4 AB domain complex shows that despite the differences in EF4, which is ion bound in the CaM:Kv7.1 complex but empty in the Apo/CaM Kv7.4 complex, bo[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
29429937
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"R555 is located on the HC helix of KCNQ1, which interacts with the CaM C-lobe in the PIP2-bound state."
31883792
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"The proximal Kv7.1 C-terminus binds calmodulin (CaM) and phosphatidylinositol-4,5-bisphosphate (PIP 2 ) and recently we revealed the competition of PIP 2 with the calcified CaM N-lobe to a previously unidentified site in Kv7.1 helix B, also known to harbor a LQT mutation."
28976808
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"Similar results were obtained with the same analysis on the Xenopus KCNQ1 and CaM complex, further validating the conserved importance of Q1-R360 and Q1-P535."
33310856
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"CaM also interacts with the Kv7.1 voltage sensor domain."
| PMC
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"Functional and biochemical analysis of LQTS mutations in the KCNQ1 C-terminus showed that disruption of CaM interaction with KCNQ1 interfered with subunit assembly and that the resultant channels generated very small currents."
19333131
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"CaM binds to the C-terminal of KCNQ1 and is essential for channel folding and assembly."
31825788
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"We next conducted studies of docking to the cryo-electron microscopy (cryo-EM)-derived human KCNQ1-calmodulin structure xref ."
32641720
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"Recent cryo-electron microscopy (EM) structural studies of the full-length KCNQ1 and CaM complex revealed intricate interactions between CaM, the KCNQ1 VSD, and the membrane lipid PIP 2."
33310856
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"The underlying idea is that a perturbation of residue interactions, such as those induced by the movements of S4 gating charges (the source), spreads to other residues (nodes) via diffusion along the KCNQ1 and CaM complex (network) before they arrive at the pore (the sink)."
33310856
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"In addition, the CaM- Kv7.1 interaction may also be relevant for the regulation of I Ks gating."
24600393
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"The structural data presented here, namely the Kv7.1 proximal C terminus bound to CaM, provide us with a near atomic resolution picture of this module."
25441029
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"Functional and biochemical analysis of LQTS mutations in the KCNQ1 C-terminus showed that disruption of CaM interaction with KCNQ1 interfered with subunit assembly and that the resultant channels generated very small currents."
19333131
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"The final network thus encodes all residues (nodes) and interactions (edges) within the KCNQ1 and CaM complex."
33310856
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"Our data indicate that in healthy individuals, CaM binding to KCNQ1 is essential for correct channel folding and assembly and for conferring Ca(2+)-sensitive IKS-current stimulation, which increases the cardiac repolarization reserve and hence prevents the risk of ventricular arrhythmias."
16556865
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"A redox motif flanking Cys(445) and the interaction of KCNQ1 with calmodulin are required for preferential S-nitrosylation of Cys(445)."
19124472
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"Our data indicate that in healthy individuals, CaM binding to KCNQ1 is essential for correct channel folding and assembly and for conferring Ca (2+)-sensitive IKS-current stimulation, which increases the cardiac repolarization reserve and hence prevents the risk of ventricular arrhythmias."
16556865
sparser
"Relevant to this question, CaM’s binding target can affect CaM’s affinity for Ca 2+ , so that it is possible that when CaM associates with the Kv7.1 proximal C terminus, CaM N lobe Ca 2+ affinity inc[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
25441029