Journal article
Troponin C/calmodulin chimeras as erythrocyte plasma membrane Ca2+-ATPase activators
The international journal of biochemistry & cell biology, Vol.38(2), pp.209-221
02/2006
Handle:
https://hdl.handle.net/2376/113328
PMID: 16213185
Abstract
Calmodulin (CaM) and troponin C (TnC) are EF-hand proteins that play fundamentally different roles in animal physiology. TnC has a very low affinity for the plasma membrane Ca2+-ATPase and is a poor substitute for CaM in increasing the enzyme's affinity for Ca2+ and the rate of ATP hydrolysis. We use a series of recombinant TnC (rTnC)/CaM chimeras to clarify the importance of the CaM carboxyl-terminal domain in the activation of the plasma membrane Ca2+-ATPase. The rTnC/CaM chimera, in which the carboxyl-terminal domain of TnC is replaced by that of CaM, has the same ability as CaM to bind and transmit the signal to Ca2+ sites on the enzyme. There is no further functional gain when the amino-terminal domain is modified to make the rTnC/CaM chimera more CaM-like. To identify which regions of the carboxyl-terminal domain of CaM are responsible for these effects, we constructed the chimeras rTnC/3CaM and rTnC/4CaM, where only one-half of the C-terminal domain of CaM (residues 85-112 or residues 113-148) replaces the corresponding region in rTnC. Neither rTnC/3CaM nor rTnC/4CaM can mimic CaM in its affinity for the enzyme. Nevertheless, with respect to the signal transduction process, rTnC/4CaM, but not rTnC/3CaM, shows the same behaviour as CaM. We conclude that the whole C-terminal domain is required for binding to the enzyme while Ca2+-binding site 4 of CaM bears all the requirements to increase Ca2+ binding at PMCA sites. Such mechanism of binding and activation is distinct from that proposed for most other CaM targets. Furthermore, we suggest that Ala128 and Met124 from CaM site 4 may play a crucial role in discriminating CaM from TnC.
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Details
- Title
- Troponin C/calmodulin chimeras as erythrocyte plasma membrane Ca2+-ATPase activators
- Creators
- Elizabeth Fidalgo da Silva - Instituto de Bioquímica Médica, Centro de Ciências da Saúde, Universidade Federal do Rio de Janeiro, Cidade Universitária, 21941-590 Rio de Janeiro, RJ, BrazilMônica M FreireHector BarrabinMartha M SorensonSvetlana TikunovaJ David JohnsonMurali ChandraJoyce R PearlstoneHelena M Scofano
- Publication Details
- The international journal of biochemistry & cell biology, Vol.38(2), pp.209-221
- Academic Unit
- Integrative Physiology and Neuroscience, Department of
- Publisher
- Netherlands
- Identifiers
- 99900548058801842
- Language
- English
- Resource Type
- Journal article