Intrinsically disordered HAX-1 regulates Ca2+ cycling by interacting with lipid membranes and the phospholamban cytoplasmic region

Research output: Contribution to journalArticle

Authors

External Institution(s)

  • University of Minnesota Twin Cities
  • Loyola University Chicago
  • Peking University

Details

Original languageEnglish (US)
Article number183034
JournalBiochimica et Biophysica Acta - Biomembranes
Volume1862
Issue number1
StatusPublished - Jan 1 2020
Peer-reviewedYes

Abstract

Hematopoietic-substrate-1 associated protein X-1 (HAX-1) is a 279 amino acid protein expressed ubiquitously. In cardiac muscle, HAX-1 was found to modulate the sarcoendoplasmic reticulum calcium ATPase (SERCA) by shifting its apparent Ca2+ affinity (pCa). It has been hypothesized that HAX-1 binds phospholamban (PLN), enhancing its inhibitory function on SERCA. HAX-1 effects are reversed by cAMP-dependent protein kinase A that phosphorylates PLN at Ser16. To date, the molecular mechanisms for HAX-1 regulation of the SERCA/PLN complex are still unknown. Using enzymatic, in cell assays, circular dichroism, and NMR spectroscopy, we found that in the absence of a binding partner HAX-1 is essentially disordered and adopts a partial secondary structure upon interaction with lipid membranes. Also, HAX-1 interacts with the cytoplasmic region of monomeric and pentameric PLN as detected by NMR and in cell FRET assays, respectively. We propose that the regulation of the SERCA/PLN complex by HAX-1 is mediated by its interactions with lipid membranes, adding another layer of control in Ca2+ homeostatic balance in the heart muscle.

    Research areas

  • HAX-1, Intrinsically disordered proteins, NMR spectroscopy, Phospholamban, Protein-membrane interactions

Citation formats

APA

Larsen, E. K., Weber, D. K., Wang, S., Gopinath, T., Blackwell, D. J., Dalton, M. P., ... Veglia, G. (2020). Intrinsically disordered HAX-1 regulates Ca2+ cycling by interacting with lipid membranes and the phospholamban cytoplasmic region. Biochimica et Biophysica Acta - Biomembranes, 1862(1), [183034]. https://doi.org/10.1016/j.bbamem.2019.183034

Harvard

Larsen, EK, Weber, DK, Wang, S, Gopinath, T, Blackwell, DJ, Dalton, MP, Robia, SL, Gao, J & Veglia, G 2020, 'Intrinsically disordered HAX-1 regulates Ca2+ cycling by interacting with lipid membranes and the phospholamban cytoplasmic region', Biochimica et Biophysica Acta - Biomembranes, vol. 1862, no. 1, 183034. https://doi.org/10.1016/j.bbamem.2019.183034