Reversal of Phospholamban Inhibition of the Sarco(endo)plasmic Reticulum Ca2+-ATPase (SERCA) Using Short, Protein-interacting RNAs and Oligonucleotide Analogs

The sarco(endo)plasmic reticulum Ca2+-ATPase (SERCA) and phospholamban (PLN) complex regulates heart relaxation through its removal of cytosolic Ca2+ during diastole. Dysfunction of this complex has been related to many heart disorders and is therefore a key pharmacological target. There are current...

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Bibliographic Details
Published in:The Journal of biological chemistry 2016-10, Vol.291 (41), p.21510-21518
Main Authors: Soller, Kailey J., Yang, Jing, Veglia, Gianluigi, Bowser, Michael T.
Format: Article
Language:English
Subjects:
calcium ATPase (SERCA)
Calcium-Binding Proteins - chemistry
Calcium-Binding Proteins - genetics
Calcium-Binding Proteins - metabolism
cardiomyopathy
fluorescence anisotropy
Humans
microRNA (miRNA)
MicroRNAs - chemistry
MicroRNAs - genetics
MicroRNAs - metabolism
oligonucleotide analogs
Oligonucleotides - chemistry
Oligonucleotides - genetics
Phospholamban (PLN)
protein complex
protein-nucleic acid interaction
RNA
RNA-protein interaction
Sarcoplasmic Reticulum Calcium-Transporting ATPases - chemistry
Sarcoplasmic Reticulum Calcium-Transporting ATPases - genetics
Sarcoplasmic Reticulum Calcium-Transporting ATPases - metabolism
structure-function
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Summary:The sarco(endo)plasmic reticulum Ca2+-ATPase (SERCA) and phospholamban (PLN) complex regulates heart relaxation through its removal of cytosolic Ca2+ during diastole. Dysfunction of this complex has been related to many heart disorders and is therefore a key pharmacological target. There are currently no therapeutics that directly target either SERCA or PLN. It has been previously reported that single-stranded DNA binds PLN with strong affinity and relieves inhibition of SERCA in a length-dependent manner. In the current article, we demonstrate that RNAs and single-stranded oligonucleotide analogs, or xeno nucleic acids (XNAs), also bind PLN strongly (Kd
ISSN:0021-9258
1083-351X
DOI:10.1074/jbc.M116.738807