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Calmodulin complexes with brain and muscle creatine kinase peptides

Sprenger, Janina LU ; Trifan, Anda ; Patel, Neal ; Vanderbeck, Ashley ; Bredfelt, Jenny ; Tajkhorshid, Emad ; Rowlett, Roger ; Lo Leggio, Leila ; Åkerfeldt, Karin S. LU and Linse, Sara LU (2021) In Current Research in Structural Biology 3. p.121-132
Abstract

Calmodulin (CaM) is a ubiquitous Ca2+ sensing protein that binds to and modulates numerous target proteins and enzymes during cellular signaling processes. A large number of CaM-target complexes have been identified and structurally characterized, revealing a wide diversity of CaM-binding modes. A newly identified target is creatine kinase (CK), a central enzyme in cellular energy homeostasis. This study reports two high-resolution X-ray structures, determined to 1.24 ​Å and 1.43 ​Å resolution, of calmodulin in complex with peptides from human brain and muscle CK, respectively. Both complexes adopt a rare extended binding mode with an observed stoichiometry of 1:2 CaM:peptide, confirmed by isothermal titration calorimetry,... (More)

Calmodulin (CaM) is a ubiquitous Ca2+ sensing protein that binds to and modulates numerous target proteins and enzymes during cellular signaling processes. A large number of CaM-target complexes have been identified and structurally characterized, revealing a wide diversity of CaM-binding modes. A newly identified target is creatine kinase (CK), a central enzyme in cellular energy homeostasis. This study reports two high-resolution X-ray structures, determined to 1.24 ​Å and 1.43 ​Å resolution, of calmodulin in complex with peptides from human brain and muscle CK, respectively. Both complexes adopt a rare extended binding mode with an observed stoichiometry of 1:2 CaM:peptide, confirmed by isothermal titration calorimetry, suggesting that each CaM domain independently binds one CK peptide in a Ca2+-depended manner. While the overall binding mode is similar between the structures with muscle or brain-type CK peptides, the most significant difference is the opposite binding orientation of the peptides in the N-terminal domain. This may extrapolate into distinct binding modes and regulation of the full-length CK isoforms. The structural insights gained in this study strengthen the link between cellular energy homeostasis and Ca2+-mediated cell signaling and may shed light on ways by which cells can ‘fine tune’ their energy levels to match the spatial and temporal demands.

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; ; ; ; ; ; ; ; and
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
Calcium signaling, Calmodulin X-ray structure, Cellular energy metabolism, Enzyme regulation, Isothermal titration calorimetry
in
Current Research in Structural Biology
volume
3
pages
12 pages
publisher
Elsevier
external identifiers
  • scopus:85107941446
  • pmid:34235492
ISSN
2665-928X
DOI
10.1016/j.crstbi.2021.05.001
language
English
LU publication?
yes
id
96d01d69-eb85-4810-a53d-54ec425ac2be
date added to LUP
2021-07-14 14:53:20
date last changed
2024-04-20 08:31:59
@article{96d01d69-eb85-4810-a53d-54ec425ac2be,
  abstract     = {{<p>Calmodulin (CaM) is a ubiquitous Ca<sup>2+</sup> sensing protein that binds to and modulates numerous target proteins and enzymes during cellular signaling processes. A large number of CaM-target complexes have been identified and structurally characterized, revealing a wide diversity of CaM-binding modes. A newly identified target is creatine kinase (CK), a central enzyme in cellular energy homeostasis. This study reports two high-resolution X-ray structures, determined to 1.24 ​Å and 1.43 ​Å resolution, of calmodulin in complex with peptides from human brain and muscle CK, respectively. Both complexes adopt a rare extended binding mode with an observed stoichiometry of 1:2 CaM:peptide, confirmed by isothermal titration calorimetry, suggesting that each CaM domain independently binds one CK peptide in a Ca<sup>2+</sup>-depended manner. While the overall binding mode is similar between the structures with muscle or brain-type CK peptides, the most significant difference is the opposite binding orientation of the peptides in the N-terminal domain. This may extrapolate into distinct binding modes and regulation of the full-length CK isoforms. The structural insights gained in this study strengthen the link between cellular energy homeostasis and Ca<sup>2+</sup>-mediated cell signaling and may shed light on ways by which cells can ‘fine tune’ their energy levels to match the spatial and temporal demands.</p>}},
  author       = {{Sprenger, Janina and Trifan, Anda and Patel, Neal and Vanderbeck, Ashley and Bredfelt, Jenny and Tajkhorshid, Emad and Rowlett, Roger and Lo Leggio, Leila and Åkerfeldt, Karin S. and Linse, Sara}},
  issn         = {{2665-928X}},
  keywords     = {{Calcium signaling; Calmodulin X-ray structure; Cellular energy metabolism; Enzyme regulation; Isothermal titration calorimetry}},
  language     = {{eng}},
  pages        = {{121--132}},
  publisher    = {{Elsevier}},
  series       = {{Current Research in Structural Biology}},
  title        = {{Calmodulin complexes with brain and muscle creatine kinase peptides}},
  url          = {{http://dx.doi.org/10.1016/j.crstbi.2021.05.001}},
  doi          = {{10.1016/j.crstbi.2021.05.001}},
  volume       = {{3}},
  year         = {{2021}},
}