Backbone and side-chain resonance assignments of (Ca 2+ ) 4 -calmodulin bound to beta calcineurin A CaMBD peptide

C Andrew Fowler; Maria F Núñez Hernandez; Susan E O'Donnell; Liping Yu; Madeline A Shea

doi:10.1007/s12104-017-9762-7

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Backbone and side-chain resonance assignments of (Ca 2+ ) 4 -calmodulin bound to beta calcineurin A CaMBD peptide

C Andrew Fowler, Maria F Núñez Hernandez, Susan E O'Donnell, Liping Yu and Madeline A Shea

Biomolecular NMR assignments, Vol.11(2), pp.275-280

10/2017

DOI: 10.1007/s12104-017-9762-7

PMCID: PMC5693717

PMID: 28815458

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https://www.ncbi.nlm.nih.gov/pmc/articles/5693717View

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Abstract

Calcineurin (CaN) is a heterodimeric and highly conserved serine/threonine phosphatase (PP2B) that plays a critical role in coupling calcium signals to physiological processes including embryonic cardiac development, NF-AT-regulated gene expression in immune responses, and apoptosis. The catalytic subunit (CaN ) has three isoforms (α, β, and γ,) in humans and seven isoforms in Paramecium. In all eukaryotes, the EF-hand protein calmodulin (CaM) regulates CaN activity in a calcium-dependent manner. The N- and C-domains of CaM (CaM and CaM ) recognize a CaM-binding domain (CaMBD) within an intrinsically disordered region of CaN that precedes the auto-inhibitory domain (AID) of CaN . Here we present nearly complete H, C, and N resonance assignments of (Ca ) -CaM bound to a peptide containing the CaMBD sequence in the beta isoform of CaN (βCaN -CaMBDp). Its secondary structure elements predicted from the assigned chemical shifts were in good agreement with those observed in the high-resolution structures of (Ca ) -CaM bound to CaMBDs of multiple enzymes. Based on the reported literature, the CaMBD of the α isoform of CaN can bind to CaM in two opposing orientations which may influence the regulatory function of CaM. Because a high resolution structure of (Ca ) -CaM bound to βCaN -CaMBDp has not been reported, our studies serve as a starting point for determining the solution structure of this complex. This will demonstrate the preferred orientation of (Ca ) -CaM on the CaMBD as well as the orientations of CaM and CaM relative to each other and to the AID of βCaN .

Amino Acid Sequence

Peptide Fragments - chemistry

Peptide Fragments - metabolism

Calmodulin - metabolism

Calcium - metabolism

Calcineurin - chemistry

Nuclear Magnetic Resonance, Biomolecular

Protein Binding

Details

Title: Subtitle: Backbone and side-chain resonance assignments of (Ca 2+ ) 4 -calmodulin bound to beta calcineurin A CaMBD peptide
Creators: C Andrew Fowler - NMR Facility, Roy J. and Lucille A. Carver College of Medicine, University of Iowa, Iowa, IA, 52242-1109, USA
Maria F Núñez Hernandez - Department of Biochemistry, Roy J. and Lucille A. Carver College of Medicine, University of Iowa, Iowa, IA, 52242-1109, USA
Susan E O'Donnell - Department of Biochemistry, Roy J. and Lucille A. Carver College of Medicine, University of Iowa, Iowa, IA, 52242-1109, USA
Liping Yu - Department of Biochemistry, Roy J. and Lucille A. Carver College of Medicine, University of Iowa, Iowa, IA, 52242-1109, USA
Madeline A Shea - Department of Biochemistry, Roy J. and Lucille A. Carver College of Medicine, University of Iowa, Iowa, IA, 52242-1109, USA. madeline-shea@uiowa.edu
Resource Type: Journal article
Publication Details: Biomolecular NMR assignments, Vol.11(2), pp.275-280
DOI: 10.1007/s12104-017-9762-7
PMID: 28815458
PMCID: PMC5693717
NLM abbreviation: Biomol NMR Assign
ISSN: 1874-2718
eISSN: 1874-270X
Publisher: Netherlands
Grant note: R01 GM57001 / National Institutes of Health (US) R25 GM058939 / NIGMS NIH HHS R25 GM058939 / National Institutes of Health (US) 12GRNT12050395 / American Heart Association R01 GM057001 / NIGMS NIH HHS
Language: English
Date published: 10/2017
Academic Unit: Molecular Physiology and Biophysics; Iowa Neuroscience Institute; Biochemistry and Molecular Biology; Medicine Administration
Record Identifier: 9984024506002771

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