Skip to content
DraconiticResearch
Search Sources API
190,869 studies31 sourcesUpdated 55 min ago
Peer-reviewedCC BY 4.0eLife

Molecular and functional analysis of calcium binding by a cancer-linked calreticulin mutant

  • Ishmael Nii Ayibontey Tagoe1,2
  • Amanpreet Kaur1
  • Osbourne Quaye2
  • Emmanuel Ayitey Tagoe3
  • Nicole M Koropatkin1
  • Leslie S Satin4
  • Malini Raghavan1
4 affiliations
  1. 1Department of Microbiology and Immunology, University of Michigan Medical School, Ann Arbor, United States
  2. 2West African Centre for Cell Biology of Infectious Pathogens, Departments of Biochemistry, Cell and Molecular Biology, University of Ghana, Accra, Ghana
  3. 3Medical Laboratory Sciences, University of Ghana, Accra, Ghana
  4. 4Department of Pharmacology, University of Michigan Medical School, Ann Arbor, United States
Read full textPDFDOICite

Abstract

Calreticulin (CRT) is an endoplasmic reticulum (ER) chaperone with low-affinity calcium-binding sites in its C-terminal domain. This region is altered by somatic mutations in the CRT gene (CALR), which drive a subset of myeloproliferative neoplasms (MPNs). Perturbations in ER calcium storage and signaling are reported for the MPN type I mutant, CRTDel52, and are linked to disease pathogenesis. Using recombinant CRT proteins, we found similar low-affinity calcium-binding characteristics for wild-type CRT and CRTDel52, as determined by isothermal titration calorimetry (ITC). Residues 340–349, conserved in both wild-type CRT and CRTDel52, contribute to binding. Furthermore, ER and cytosolic calcium levels, and store-operated calcium entry (SOCE), were comparable in CRT knockout (CRT-KO) cells reconstituted with wild-type CRT or CRTDel52. Notably, the CRT-KO induces expression of multiple ER proteins known to contain low-affinity calcium-binding sites or regulate ER calcium levels. Overall, these findings indicate that CRTDel52 retains at least some low-affinity calcium-binding capacity and that CRT deficiency induces compensatory cellular changes that maintain ER calcium homeostasis.

Related

  1. A chemical-genetic system for calreticulin exposure on cancer cells reveals immune-dependent antitumor effects
    Liwei Zhao, Misha Mao, Zhe Shen +5
    Cell Death and DifferentiationPeer-reviewedCC BY 4.0Full textImmunologyHAL
  2. Gene-family-dependent thermodynamic effects of oncogenic mutations on nucleosome-DNA binding stability: a comparative molecular dynamics study across 22 cancer hotspots
    S. Freudenberger, E. Boczko, S. Goel +1
    bioRxivPreprintCC BYFull textBioinformatics & computational biologybioRxiv
  3. Neuroprotective potential of vitamin D3 against glucocorticoid-induced neurotoxicity: Focus on calcium-binding proteins and neuroinflammation in a rat model
    Ihor Shymanskyi, Olha Lisakovska, Anna Khomenko +2
    IBRO neuroscience reportsPeer-reviewedCC BYFull textNeuroscienceEurope PMC
  4. Accelerating Molecular Dynamics with Hydrogen Mass Repartitioning to Prioritize Immunogenic Neoantigens for Cancer Vaccines through Peptide HLA Binding Free Energy Calculations
    D. A. Amaya-Ramirez, J. B. Florez-Suarez, J. D. Mora-Fonseca +1
    bioRxivPreprintCC BYFull textImmunologybioRxiv
  5. Calcium-dependent conformational transitions and ligand binding regulation of C-reactive protein: a comprehensive review
    Bin Cheng, Zhi-Xin Yao, Guo-Qiang Wu
    Frontiers in ImmunologyPeer-reviewedCC BY 4.0Full textImmunologyPMCCrossrefEurope PMC

Cite

BibTeXRIS
BibTeX
@article{tagoe2026molecular,
  title = {{Molecular and functional analysis of calcium binding by a cancer-linked calreticulin mutant}},
  author = {Ishmael Nii Ayibontey Tagoe and Amanpreet Kaur and Osbourne Quaye and Emmanuel Ayitey Tagoe and Nicole M Koropatkin and Leslie S Satin and Malini Raghavan},
  journal = {eLife},
  year = {2026},
  month = oct,
  doi = {10.7554/elife.109647},
  url = {https://elifesciences.org/articles/109647},
  note = {CC BY 4.0},
}
RIS
TY  - JOUR
TI  - Molecular and functional analysis of calcium binding by a cancer-linked calreticulin mutant
AU  - Ishmael Nii Ayibontey Tagoe
AU  - Amanpreet Kaur
AU  - Osbourne Quaye
AU  - Emmanuel Ayitey Tagoe
AU  - Nicole M Koropatkin
AU  - Leslie S Satin
AU  - Malini Raghavan
PY  - 2026
DA  - 2026/10/29
JO  - eLife
DO  - 10.7554/elife.109647
UR  - https://elifesciences.org/articles/109647
AB  - Calreticulin (CRT) is an endoplasmic reticulum (ER) chaperone with low-affinity calcium-binding sites in its C-terminal domain. This region is altered by somatic mutations in the CRT gene (CALR), which drive a subset of myeloproliferative neoplasms (MPNs). Perturbations in ER calcium storage and signaling are reported for the MPN type I mutant, CRTDel52, and are linked to disease pathogenesis. Using recombinant CRT proteins, we found similar low-affinity calcium-binding characteristics for wild-type CRT and CRTDel52, as determined by isothermal titration calorimetry (ITC). Residues 340–349, conserved in both wild-type CRT and CRTDel52, contribute to binding. Furthermore, ER and cytosolic calcium levels, and store-operated calcium entry (SOCE), were comparable in CRT knockout (CRT-KO) cells reconstituted with wild-type CRT or CRTDel52. Notably, the CRT-KO induces expression of multiple ER proteins known to contain low-affinity calcium-binding sites or regulate ER calcium levels. Overall, these findings indicate that CRTDel52 retains at least some low-affinity calcium-binding capacity and that CRT deficiency induces compensatory cellular changes that maintain ER calcium homeostasis.
SN  - 2050-084X
ER  -