Structural and dynamic basis of phospholamban and sarcolipin inhibition of Ca2+-ATPase

Nathaniel Traaseth, Kim N. Ha, Raffaello Verardi, Lei Shi, Jarrod J. Buffy, Larry R. Masterson, Gianluigi Veglia

Research output: Contribution to journalArticle

Abstract

Phospholamban (PLN) and sarcolipin (SLN) are two single-pass membrane proteins that regulate Ca2+-ATPase (SERCA), an ATP-driven pump that translocates calcium ions into the lumen of the sarcoplasmic reticulum, initiating muscle relaxation. Both proteins bind SERCA through intramembrane interactions, impeding calcium translocation. While phosphorylation of PLN at Ser-16 and/or Thr-17 reestablishes calcium flux, the regulatory mechanism of SLN remains elusive. SERCA has been crystallized in several different states along the enzymatic reaction coordinates, providing remarkable mechanistic information; however, the lack of high-resolution crystals in the presence of PLN and SLN limits the current understanding of the regulatory mechanism. This brief review offers a survey of our hybrid structural approach using solution and solid-state NMR methodologies to understand SERCA regulation from the point of view of PLN and SLN. These results have improved our understanding of the calcium translocation process and are the basis for designing new therapeutic approaches to ameliorate muscle malfunctions.

Original languageEnglish (US)
Pages (from-to)3-13
Number of pages11
JournalBiochemistry
Volume47
Issue number1
DOIs
StatePublished - Jan 8 2008

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Calcium-Transporting ATPases
Calcium
Muscle
Phosphorylation
Muscle Relaxation
Sarcoplasmic Reticulum
Membrane Proteins
Adenosine Triphosphate
Nuclear magnetic resonance
Pumps
Ions
Fluxes
Muscles
Crystals
sarcolipin
phospholamban
Proteins
Therapeutics

ASJC Scopus subject areas

  • Biochemistry

Cite this

Traaseth, N., Ha, K. N., Verardi, R., Shi, L., Buffy, J. J., Masterson, L. R., & Veglia, G. (2008). Structural and dynamic basis of phospholamban and sarcolipin inhibition of Ca2+-ATPase. Biochemistry, 47(1), 3-13. https://doi.org/10.1021/bi701668v

Structural and dynamic basis of phospholamban and sarcolipin inhibition of Ca2+-ATPase. / Traaseth, Nathaniel; Ha, Kim N.; Verardi, Raffaello; Shi, Lei; Buffy, Jarrod J.; Masterson, Larry R.; Veglia, Gianluigi.

In: Biochemistry, Vol. 47, No. 1, 08.01.2008, p. 3-13.

Research output: Contribution to journalArticle

Traaseth, N, Ha, KN, Verardi, R, Shi, L, Buffy, JJ, Masterson, LR & Veglia, G 2008, 'Structural and dynamic basis of phospholamban and sarcolipin inhibition of Ca2+-ATPase', Biochemistry, vol. 47, no. 1, pp. 3-13. https://doi.org/10.1021/bi701668v
Traaseth, Nathaniel ; Ha, Kim N. ; Verardi, Raffaello ; Shi, Lei ; Buffy, Jarrod J. ; Masterson, Larry R. ; Veglia, Gianluigi. / Structural and dynamic basis of phospholamban and sarcolipin inhibition of Ca2+-ATPase. In: Biochemistry. 2008 ; Vol. 47, No. 1. pp. 3-13.
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