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Chapitre D'ouvrage Année : 2015

Functional and structural insights into Sarcolipin, a regulator of the Sarco-endoplasmic reticulum Ca2+-ATPases

Résumé

Sarcolipin (SLN), a transmembrane peptide from sarcoplasmic reticulum, is one of the major proteins involved in the muscle contraction/relaxation process. A number of enzymological studies have underlined its regulatory role in connection with the SERCA1a activity. Indeed, SLN folds as a unique transmembrane helix and binds to SERCA1a in a groove close to transmembrane helices M2, M6, and M9, as proposed initially by cross-linking experiments and recently detailed in the 3D structures of the SLN–Ca2+-ATPase complex. In addition, association of SLN with SERCAs may depend on its phosphorylation. SLN possesses a peculiar C-terminus (RSYQY) critical for the regulation of the ATPases. This luminal tail appears to be essential for addressing SLN to the ER membrane. Moreover, we recently demonstrated that some SLN isoforms are acylated on cysteine 9, a feature which remained unnoticed so far even in the recent crystal structures of the SLN–SERCA1a complex. The removal of the fatty acid chain was shown to increase the activity of the membrane-embedded Ca2+-ATPase by about 20 %. The exact functional and structural role of this post-translational modification is presently unknown. Recent data are in favor of a key regulator role of SLN in muscle-based thermogenesis in mammals. The possible link of SLN to heat production could occur through an uncoupling of the SERCA1a-mediated ATP hydrolysis from calcium transport. Considering those particular features and the fact that SLN is not expressed at the same level in different tissues, the role of SLN and its exact mechanism of regulation remain sources of interrogation.
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hal-02393614 , version 1 (22-08-2022)

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Thomas Barbot, Cédric Montigny, Paulette Decottignies, Marc Le Maire, Christine Jaxel, et al.. Functional and structural insights into Sarcolipin, a regulator of the Sarco-endoplasmic reticulum Ca2+-ATPases. Chakraborti, Sajal; Dhalla, Naranjan S. Regulation of Ca2+-ATPases,V-ATPases and F-ATPases, 14, Springer International Publishing, pp.153-186, 2015, Advances in Biochemistry in Health and Disease, 978-3-319-24778-6 (print) 978-3-319-24780-9 (e-book). ⟨10.1007/978-3-319-24780-9_10⟩. ⟨hal-02393614⟩
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