Cargando…

Functional and Structural Characterization of a Eurytolerant Calsequestrin from the Intertidal Teleost Fundulus heteroclitus

Calsequestrins (CSQ) are high capacity, medium affinity, calcium-binding proteins present in the sarcoplasmic reticulum (SR) of cardiac and skeletal muscles. CSQ sequesters Ca(2+) during muscle relaxation and increases the Ca(2+)-storage capacity of the SR. Mammalian CSQ has been well studied as a m...

Descripción completa

Detalles Bibliográficos
Autores principales: Whittington, A. Carl, Nienow, Tatyana E., Whittington, Christi L., Fort, Timothy J., Grove, Theresa J.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2012
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3511267/
https://www.ncbi.nlm.nih.gov/pubmed/23226387
http://dx.doi.org/10.1371/journal.pone.0050801
Descripción
Sumario:Calsequestrins (CSQ) are high capacity, medium affinity, calcium-binding proteins present in the sarcoplasmic reticulum (SR) of cardiac and skeletal muscles. CSQ sequesters Ca(2+) during muscle relaxation and increases the Ca(2+)-storage capacity of the SR. Mammalian CSQ has been well studied as a model of human disease, but little is known about the environmental adaptation of CSQ isoforms from poikilothermic organisms. The mummichog, Fundulus heteroclitus, is an intertidal fish that experiences significant daily and seasonal environmental fluctuations and is an interesting study system for investigations of adaptation at the protein level. We determined the full-length coding sequence of a CSQ isoform from skeletal muscle of F. heteroclitus (FCSQ) and characterized the function and structure of this CSQ. The dissociation constant (K(d)) of FCSQ is relatively insensitive to changes in temperature and pH, thus indicating that FCSQ is a eurytolerant protein. We identified and characterized a highly conserved salt bridge network in FCSQ that stabilizes the formation of front-to-front dimers, a process critical to CSQ function. The functional profile of FCSQ correlates with the natural history of F. heteroclitus suggesting that the eurytolerant function of FCSQ may be adaptive.