Evidence map›Paper›PMID 21652722›Full record

ArticleThe Journal of biological chemistry2011

Double mutant cycle analysis identified a critical leucine residue in the IIS4S5 linker for the activation of the Ca(V)2.3 calcium channel.

Sébastien Wall-Lacelle, Md Israil Hossain, Rémy Sauvé, Rikard Blunck, Lucie Parent

Abstract read
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Article in The Journal of biological chemistry, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.

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0cells of the map it votes in
26citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

26 citing papers in PubMed.

  1. Article
  2. Review
  3. Article
  4. Calcium channel gating.Pflugers Archiv : European journal of physiology · 2018
    Review
  5. S4-S5 linker movement during activation and inactivation in voltage-gated KProceedings of the National Academy of Sciences of the United States of America · 2018
    Article
  6. Article
  7. Proteolytic cleavage of the hydrophobic domain in the CaThe Journal of biological chemistry · 2017
    Article
  8. Article
  9. Article
  10. Article
  11. Article
  12. Article
  13. Review
  14. A systematic survey of an intragenic epistatic landscape.Molecular biology and evolution · 2015
    Article
  15. Article
  16. Article
  17. Article
  18. Article
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  20. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

5 authors.

Sébastien Wall-LacelleDepartment of Physiologie, Membrane Protein Research Group, Université de Montréal, Montréal, Quebec H3C 3J7, Canada.
Md Israil Hossain
Rémy Sauvé
Rikard Blunck
Lucie Parent

Funding

Canadian Institutes of Health Research MOP13390
6 · The paper itself

Abstract

Mutations in distal S6 were shown to significantly alter the stability of the open state of Ca(V)2.3 (Raybaud, A., Baspinar, E. E., Dionne, F., Dodier, Y., Sauvé, R., and Parent, L. (2007) J. Biol. Chem. 282, 27944-27952). By analogy with K(V) channels, we tested the hypothesis that channel activation involves electromechanical coupling between S6 and the S4S5 linker in Ca(V)2.3. Among the 11 positions tested in the S4S5 linker of domain II, mutations of the leucine residue at position 596 were found to destabilize significantly the closed state with a -50 mV shift in the activation potential and a -20 mV shift in its charge-voltage relationship as compared with Ca(V)2.3 wt. A double mutant cycle analysis was performed by introducing pairs of glycine residues between S4S5 and S6 of Domain II. Strong coupling energies (ΔΔG(interact) > 2 kcal mol(-1)) were measured for the activation gating of 12 of 39 pairs of mutants. Leu-596 (IIS4S5) was strongly coupled with distal residues in IIS6 from Leu-699 to Asp-704. In particular, the double mutant L596G/I701G showed strong cooperativity with a ΔΔG(interact) ≈6 kcal mol(-1) suggesting that both positions contribute to the activation gating of the channel. Altogether, our results highlight the role of a leucine residue in S4S5 and provide the first series of evidence that the IIS4S5 and IIS6 regions are energetically coupled during the activation of a voltage-gated Ca(V) channel.

Indexed as

Point MutationAmino Acid SequenceCalcium Channels, R-TypeCation Transport ProteinsDNA, RecombinantHumansLeucineMolecular Sequence DataPatch-Clamp TechniquesCACNA1E protein, humanCalcium Channels, R-TypeCation Transport ProteinsDNA, RecombinantLeucine

Identifiers

PMID21652722
PMCPMC3149313

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.