ArticleThe Journal of biological chemistry2010
Essential role of the CBD1-CBD2 linker in slow dissociation of Ca2+ from the regulatory two-domain tandem of NCX1.
Article in The Journal of biological chemistry, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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19 citing papers in PubMed, 52 citations in OpenAlex.
- The NaThe Journal of veterinary medical science · 2026Review
- Structural dynamics of NaCommunications biology · 2024Article
- Structural mechanisms of the human cardiac sodium-calcium exchanger NCX1.Nature communications · 2023Article
- Structure-Based Function and Regulation of NCX Variants: Updates and Challenges.International journal of molecular sciences · 2022Review
- Modulation of the cardiac NaCell calcium · 2020Review
- Structure-based dynamic arrays in regulatory domains of sodium-calcium exchanger (NCX) isoforms.Scientific reports · 2017Article
- Modeling NaJournal of molecular and cellular cardiology · 2016Article
- Structural Features of Ion Transport and Allosteric Regulation in Sodium-Calcium Exchanger (NCX) Proteins.Frontiers in physiology · 2016Review
- Na+/Ca2+ exchange and Na+/K+-ATPase in the heart.The Journal of physiology · 2015Review
- Article
- Article
- Sodium-calcium exchangers (NCX): molecular hallmarks underlying the tissue-specific and systemic functions.Pflugers Archiv : European journal of physiology · 2014Review
- Population shift underlies Ca2+-induced regulatory transitions in the sodium-calcium exchanger (NCX).The Journal of biological chemistry · 2013Article
- Article
- Structural basis of the Ca2+ inhibitory mechanism of Drosophila Na+/Ca2+ exchanger CALX and its modification by alternative splicing.Structure (London, England : 1993) · 2011Article
- Residues 248-252 and 300-304 of the cardiac Na+/Ca2+ exchanger are involved in its regulation by phospholemman.American journal of physiology. Cell physiology · 2011Article
- Ca2+ binding alters the interdomain flexibility between the two cytoplasmic calcium-binding domains in the Na+/Ca2+ exchanger.The Journal of biological chemistry · 2011Article
- Proton-sensing Ca2+ binding domains regulate the cardiac Na+/Ca2+ exchanger.The Journal of biological chemistry · 2011Article
- Ca2+-dependent structural rearrangements within Na+-Ca2+ exchanger dimers.Proceedings of the National Academy of Sciences of the United States of America · 2011Article
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5 authors at 1 institution in 1 country.
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No grant is acknowledged in the PubMed record.
Abstract
In NCX proteins CBD1 and CBD2 domains are connected through a short linker (3 or 4 amino acids) forming a regulatory tandem (CBD12). Only three of the six CBD12 Ca(2+)-binding sites contribute to NCX regulation. Two of them are located on CBD1 (K(d) = approximately 0.2 microM), and one is on CBD2 (K(d) = approximately 5 microM). Here we analyze how the intrinsic properties of individual regulatory sites are affected by linker-dependent interactions in CBD12 (AD splice variant). The three sites of CBD12 and CBD1 + CBD2 have comparable K(d) values but differ dramatically in their Ca(2+) dissociation kinetics. CBD12 exhibits multiphasic kinetics for the dissociation of three Ca(2+) ions (k(r) = 280 s(-1), k(f) = 7 s(-1), and k(s) = 0.4 s(-1)), whereas the dissociation of two Ca(2+) ions from CBD1 (k(f) = 16 s(-1)) and one Ca(2+) ion from CBD2 (k(r) = 125 s(-1)) is monophasic. Insertion of seven alanines into the linker (CBD12-7Ala) abolishes slow dissociation of Ca(2+), whereas the kinetic and equilibrium properties of three Ca(2+) sites of CBD12-7Ala and CBD1 + CBD2 are similar. Therefore, the linker-dependent interactions in CBD12 decelerate the Ca(2+) on/off kinetics at a specific CBD1 site by 50-80-fold, thereby representing Ca(2+) "occlusion" at CBD12. Notably, the kinetic and equilibrium properties of the remaining two sites of CBD12 are "linker-independent," so their intrinsic properties are preserved in CBD12. In conclusion, the dynamic properties of three sites are specifically modified, conserved, diversified, and integrated by the linker in CBD12, thereby generating a wide range dynamic sensor.
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