Faculty Collaboration Database

Intrinsically disordered HAX-1 regulates Ca²⁺ cycling by interacting with lipid membranes and the phospholamban cytoplasmic region. Biochim Biophys Acta Biomembr 2020 Jan 01;1862(1):183034

Date

08/11/2019

Pubmed ID

31400305

Pubmed Central ID

PMC6899184

DOI

10.1016/j.bbamem.2019.183034

Scopus ID

2-s2.0-85070875364 (requires institutional sign-in at Scopus site)   11 Citations

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.

Author List

Larsen EK, Weber DK, Wang S, Gopinath T, Blackwell DJ, Dalton MP, Robia SL, Gao J, Veglia G

Author

Gopinath Tata PhD Assistant Professor in the Biophysics department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Adaptor Proteins, Signal Transducing
Animals
Calcium
Calcium-Binding Proteins
Cytoplasm
Humans
Intrinsically Disordered Proteins
Magnetic Resonance Spectroscopy
Membrane Lipids
Myocardium
Protein Structure, Secondary
Sarcoplasmic Reticulum Calcium-Transporting ATPases