Calreticulin: Challenges Posed by the Intrinsically Disordered Nature of Calreticulin to the Study of Its Function

Calreticulin is a Ca(2+)-binding chaperone protein, which resides mainly in the endoplasmic reticulum but also found in other cellular compartments including the plasma membrane. In addition to Ca(2+), calreticulin binds and regulates almost all proteins and most of the mRNAs deciding their intracel...

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Autores principales: Varricchio, Lilian, Falchi, Mario, Dall'Ora, Massimiliano, De Benedittis, Caterina, Ruggeri, Alessandra, Uversky, Vladimir N., Migliaccio, Anna Rita
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5703715/
https://www.ncbi.nlm.nih.gov/pubmed/29218307
http://dx.doi.org/10.3389/fcell.2017.00096
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author Varricchio, Lilian
Falchi, Mario
Dall'Ora, Massimiliano
De Benedittis, Caterina
Ruggeri, Alessandra
Uversky, Vladimir N.
Migliaccio, Anna Rita
author_facet Varricchio, Lilian
Falchi, Mario
Dall'Ora, Massimiliano
De Benedittis, Caterina
Ruggeri, Alessandra
Uversky, Vladimir N.
Migliaccio, Anna Rita
author_sort Varricchio, Lilian
collection PubMed
description Calreticulin is a Ca(2+)-binding chaperone protein, which resides mainly in the endoplasmic reticulum but also found in other cellular compartments including the plasma membrane. In addition to Ca(2+), calreticulin binds and regulates almost all proteins and most of the mRNAs deciding their intracellular fate. The potential functions of calreticulin are so numerous that identification of all of them is becoming a nightmare. Still the recent discovery that patients affected by the Philadelphia-negative myeloproliferative disorders essential thrombocytemia or primary myelofibrosis not harboring JAK2 mutations carry instead calreticulin mutations disrupting its C-terminal domain has highlighted the clinical need to gain a deeper understanding of the biological activity of this protein. However, by contrast with other proteins, such as enzymes or transcription factors, the biological functions of which are strictly defined by a stable spatial structure imprinted by their amino acid sequence, calreticulin contains intrinsically disordered regions, the structure of which represents a highly dynamic conformational ensemble characterized by constant changes between several metastable conformations in response to a variety of environmental cues. This article will illustrate the Theory of calreticulin as an intrinsically disordered protein and discuss the Hypothesis that the dynamic conformational changes to which calreticulin may be subjected by environmental cues, by promoting or restricting the exposure of its active sites, may affect its function under normal and pathological conditions.
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spelling pubmed-57037152017-12-07 Calreticulin: Challenges Posed by the Intrinsically Disordered Nature of Calreticulin to the Study of Its Function Varricchio, Lilian Falchi, Mario Dall'Ora, Massimiliano De Benedittis, Caterina Ruggeri, Alessandra Uversky, Vladimir N. Migliaccio, Anna Rita Front Cell Dev Biol Cell and Developmental Biology Calreticulin is a Ca(2+)-binding chaperone protein, which resides mainly in the endoplasmic reticulum but also found in other cellular compartments including the plasma membrane. In addition to Ca(2+), calreticulin binds and regulates almost all proteins and most of the mRNAs deciding their intracellular fate. The potential functions of calreticulin are so numerous that identification of all of them is becoming a nightmare. Still the recent discovery that patients affected by the Philadelphia-negative myeloproliferative disorders essential thrombocytemia or primary myelofibrosis not harboring JAK2 mutations carry instead calreticulin mutations disrupting its C-terminal domain has highlighted the clinical need to gain a deeper understanding of the biological activity of this protein. However, by contrast with other proteins, such as enzymes or transcription factors, the biological functions of which are strictly defined by a stable spatial structure imprinted by their amino acid sequence, calreticulin contains intrinsically disordered regions, the structure of which represents a highly dynamic conformational ensemble characterized by constant changes between several metastable conformations in response to a variety of environmental cues. This article will illustrate the Theory of calreticulin as an intrinsically disordered protein and discuss the Hypothesis that the dynamic conformational changes to which calreticulin may be subjected by environmental cues, by promoting or restricting the exposure of its active sites, may affect its function under normal and pathological conditions. Frontiers Media S.A. 2017-11-23 /pmc/articles/PMC5703715/ /pubmed/29218307 http://dx.doi.org/10.3389/fcell.2017.00096 Text en Copyright © 2017 Varricchio, Falchi, Dall'Ora, De Benedittis, Ruggeri, Uversky and Migliaccio. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Cell and Developmental Biology
Varricchio, Lilian
Falchi, Mario
Dall'Ora, Massimiliano
De Benedittis, Caterina
Ruggeri, Alessandra
Uversky, Vladimir N.
Migliaccio, Anna Rita
Calreticulin: Challenges Posed by the Intrinsically Disordered Nature of Calreticulin to the Study of Its Function
title Calreticulin: Challenges Posed by the Intrinsically Disordered Nature of Calreticulin to the Study of Its Function
title_full Calreticulin: Challenges Posed by the Intrinsically Disordered Nature of Calreticulin to the Study of Its Function
title_fullStr Calreticulin: Challenges Posed by the Intrinsically Disordered Nature of Calreticulin to the Study of Its Function
title_full_unstemmed Calreticulin: Challenges Posed by the Intrinsically Disordered Nature of Calreticulin to the Study of Its Function
title_short Calreticulin: Challenges Posed by the Intrinsically Disordered Nature of Calreticulin to the Study of Its Function
title_sort calreticulin: challenges posed by the intrinsically disordered nature of calreticulin to the study of its function
topic Cell and Developmental Biology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5703715/
https://www.ncbi.nlm.nih.gov/pubmed/29218307
http://dx.doi.org/10.3389/fcell.2017.00096
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