NMR resonance assignments of the DNA binding domain of mouse Junctophilin-2

Liping Yu; Duane D Hall; Weiyang Zhao; Long-Sheng Song

doi:10.1007/s12104-022-10091-6

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NMR resonance assignments of the DNA binding domain of mouse Junctophilin-2

Journal article

Peer reviewed

NMR resonance assignments of the DNA binding domain of mouse Junctophilin-2

Liping Yu, Duane D Hall, Weiyang Zhao and Long-Sheng Song

Biomolecular NMR assignments, Vol.16(2), pp.273-279

06/04/2022

DOI: 10.1007/s12104-022-10091-6

PMCID: PMC10394741

PMID: 35665900

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https://pmc.ncbi.nlm.nih.gov/articles/PMC10394741/pdf/nihms-1918942.pdfView

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Abstract

Junctophilin-2 (JP2) is a critical structural protein in the heart by stabilizing junctional membrane complexes between the plasma membrane and sarcoplasmic reticula responsible for precise Ca regulation. Such complexes are essential for efficient cardiomyocyte contraction and adaptation to altered cardiac workload conditions. Mutations in the JPH2 gene that encodes JP2 are associated with inherited cardiomyopathies and arrhythmias, and disruption of JP2 function is lethal. Interestingly, cardiac stress promotes the proteolytic cleavage of JP2 that triggers the translocation of its N-terminal fragment into the nucleus to repress maladaptive gene transcription. We previously found that the central region of JP2 is responsible for mediating direct DNA binding interactions. Recent structural studies indicate that this region serves as a structural role in the cytosolic form of JP2 by folding into a single continuous α-helix. However, the structural basis of how this DNA-binding domain interacts with DNA is not known. Here, we report the backbone and sidechain assignments of the DNA-binding domain (residues 331-413) of mouse JP2. These assignments reveal that the JP2 DNA binding domain is an intrinsically disordered protein and contains two α-helices located in the C-terminal portion of the protein. Moreover, this protein binds to DNA in a similar manner to that shown previously by electrophoretic mobility shift assays. Therefore, these assignments provide a framework for further structural studies into the interaction of this JP2 domain with DNA for the elucidation of transcriptional regulation of stress-responsive genes as well as its role in the stabilization of junctional membrane complexes.

Junctophilin

Cardiomyopathies

Junctophilin-2

Excitation–contraction coupling

Cardiomyocyte

DNA binding

Details

Title: Subtitle: NMR resonance assignments of the DNA binding domain of mouse Junctophilin-2
Creators: Liping Yu - University of Iowa
Duane D Hall - Department of Internal Medicine, Carver College of Medicine, University of Iowa, 285 Newton Road, Iowa City, IA, 52242, USA
Weiyang Zhao - University of Iowa
Long-Sheng Song - Iowa City Veterans Affairs Medical Center, Iowa City, IA, 52242, USA. long-sheng-song@uiowa.edu
Resource Type: Journal article
Publication Details: Biomolecular NMR assignments, Vol.16(2), pp.273-279
DOI: 10.1007/s12104-022-10091-6
PMID: 35665900
PMCID: PMC10394741
NLM abbreviation: Biomol NMR Assign
ISSN: 1874-2718
eISSN: 1874-270X
Grant note: R01 HL130346 / NHLBI NIH HHS
Language: English
Date published: 06/04/2022
Academic Unit: Cardiovascular Medicine; Fraternal Order of Eagles Diabetes Research Center; Biochemistry and Molecular Biology; Medicine Administration; Internal Medicine
Record Identifier: 9984288725002771

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