System Approach for Building of Calcium-Binding Sites in Proteins

Denesyuk, Alexander I.; Permyakov, Sergei E.; Johnson, Mark S.; Denessiouk, Konstantin; Permyakov, Eugene A.

doi:10.3390/biom10040588

Cited by 2 publications

(2 citation statements)

References 32 publications

(32 reference statements)

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“…Ca 2+ has therefore a lower charge density with a tendency to coordinate more interacting atoms in binding sites. Mg 2+ has a higher hydration energy than Ca 2+ 10 , and in binding sites, the distance between the divalent cation and the interacting oxygen atoms is smaller for Mg 2+ with 2.0 to 2.1 Å than for Ca 2+ with 2.3 to 2.6 Å 37 . In troponin C for example, Ca 2+ has been shown to coordinate an additional glutamate compared to Mg 2+ , which may be critical for the selectivity between these two ions and may explain the better affinity for Ca 2+ 38 .…”

Section: Discussionmentioning

confidence: 94%

Identification of the modulatory Ca²⁺binding sites of acid-sensing ion channel 1a

Molton,

Bignucolo,

Kellenberger

2023

Preprint

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Acid-sensing ion channels (ASICs) are neuronal H+-gated, Na+-permeable channels involved in learning, fear sensing, pain sensation and neurodegeneration. An increase in the extracellular Ca2+concentration shifts the pH dependence of ASIC1a to more acidic values. Here, we predicted candidate residues for Ca2+binding on ASIC1a, based on available structural information and molecular dynamics simulations; the function of channels carrying mutations of these residues was then measured. We identify several residues in cavities previously associated with pH-dependent gating, whose mutation decreased the Ca2+-induced shift in ASIC1a pH dependence, likely due to a disruption of Ca2+binding. We show also that Mg2+shares some of the binding sites with Ca2+, and that some of the Ca2+binding sites are functionally conserved in the splice variant ASIC1b. Our identification of divalent cation binding sites in ASIC1a shows how Ca2+affects ASIC1a gating, elucidating a regulatory mechanism present in many ion channels.

show abstract

Section: Discussionmentioning

confidence: 94%

Identification of the modulatory Ca²⁺binding sites of acid-sensing ion channel 1a

Molton,

Bignucolo,

Kellenberger

2023

Preprint

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“…Although the interaction of dehydrated Ca 2+ and Mg 2+ ions with proteins differ [10], those of the hydrated ions are quite similar. Magnesium interacts in binding sites generally with less atoms and at smaller distances than Ca 2+ [38]. In troponin C, for example, Ca 2+ has been shown to coordinate an additional glutamate compared with Mg 2+ , which may be critical for the selectivity between these two ions and may explain the higher affinity for Ca 2+ [39].…”

Section: Discussionmentioning

confidence: 99%

Identification of the modulatory Ca ²⁺ -binding sites of acid-sensing ion channel 1a

Molton,

Bignucolo,

Kellenberger

2024

Open Biol.

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Acid-sensing ion channels (ASICs) are neuronal Na + -permeable ion channels activated by extracellular acidification. ASICs are involved in learning, fear sensing, pain sensation and neurodegeneration. Increasing the extracellular Ca 2+ concentration decreases the H + sensitivity of ASIC1a, suggesting a competition for binding sites between H + and Ca 2+ ions. Here, we predicted candidate residues for Ca 2+ binding on ASIC1a, based on available structural information and our molecular dynamics simulations. With functional measurements, we identified several residues in cavities previously associated with pH-dependent gating, whose mutation reduced the modulation by extracellular Ca 2+ of the ASIC1a pH dependence of activation and desensitization. This occurred probably owing to a disruption of Ca 2+ binding. Our results link one of the two predicted Ca 2+ -binding sites in each ASIC1a acidic pocket to the modulation of channel activation. Mg 2+ regulates ASICs in a similar way as does Ca 2+ . We show that Mg 2+ shares some of the binding sites with Ca 2+ . Finally, we provide evidence that some of the ASIC1a Ca 2+ -binding sites are functionally conserved in the splice variant ASIC1b. Our identification of divalent cation-binding sites in ASIC1a shows how Ca 2+ affects ASIC1a gating, elucidating a regulatory mechanism present in many ion channels.

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System Approach for Building of Calcium-Binding Sites in Proteins

Cited by 2 publications

References 32 publications

Identification of the modulatory Ca²⁺binding sites of acid-sensing ion channel 1a

Identification of the modulatory Ca²⁺binding sites of acid-sensing ion channel 1a

Identification of the modulatory Ca ²⁺ -binding sites of acid-sensing ion channel 1a

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System Approach for Building of Calcium-Binding Sites in Proteins

Cited by 2 publications

References 32 publications

Identification of the modulatory Ca2+binding sites of acid-sensing ion channel 1a

Identification of the modulatory Ca2+binding sites of acid-sensing ion channel 1a

Identification of the modulatory Ca 2+ -binding sites of acid-sensing ion channel 1a

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Identification of the modulatory Ca²⁺binding sites of acid-sensing ion channel 1a

Identification of the modulatory Ca²⁺binding sites of acid-sensing ion channel 1a

Identification of the modulatory Ca ²⁺ -binding sites of acid-sensing ion channel 1a