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ET is characterized by an overproduction of platelets that can lead to thrombosis formation. Platelet overproduction occurs in megakaryocytes through a signaling pathway that could involve JAK2, MPL, or CALR proteins. CALR mutations are associated with 25\u201330% of ET patients; CALR variants must be dimerized to induce ET. We classified these variants into five classes named A to E; classes A and B are the most frequent classes in patients with ET. The dynamic properties of these five classes using structural models of CALR\u2019s C-domain were analyzed using molecular dynamics simulations. Classes A, B, and C are associated with frameshifts in the C-domain. Their dimers can be stable only if a disulfide bond is formed; otherwise, the two monomers repulse each other. Classes D and E cannot be stable as dimers due to the absence of disulfide bonds. Class E and wild-type CALR have similar dynamic properties. These results suggest that the disulfide bond newly formed in classes A, B, and C may be essential for the pathogenicity of these variants. They also underline that class E cannot be directly related to ET but corresponds to human polymorphisms.<\/jats:p>","DOI":"10.3390\/biom13030509","type":"journal-article","created":{"date-parts":[[2023,3,10]],"date-time":"2023-03-10T05:02:17Z","timestamp":1678424537000},"page":"509","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Structural and Dynamic Differences between Calreticulin Mutants Associated with Essential Thrombocythemia"],"prefix":"10.3390","volume":"13","author":[{"given":"Ragousandirane","family":"Radjasandirane","sequence":"first","affiliation":[{"name":"Universit\u00e9 Paris Cit\u00e9 and Universit\u00e9 de la R\u00e9union and Universit\u00e9 des Antilles, INSERM, BIGR, DSIMB Bioinformatics Team, F-75014 Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7112-5626","authenticated-orcid":false,"given":"Alexandre G.","family":"de Brevern","sequence":"additional","affiliation":[{"name":"Universit\u00e9 Paris Cit\u00e9 and Universit\u00e9 de la R\u00e9union and Universit\u00e9 des Antilles, INSERM, BIGR, DSIMB Bioinformatics Team, F-75014 Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,3,10]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"2391","DOI":"10.1182\/blood-2016-03-643544","article-title":"The 2016 revision to the World Health Organization classification of myeloid neoplasms and acute leukemia","volume":"127","author":"Arber","year":"2016","journal-title":"Blood"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"2786","DOI":"10.1080\/10428194.2017.1312371","article-title":"Essential thrombocythemia: A review of the clinical features, diagnostic challenges, and treatment modalities in the era of molecular discovery","volume":"58","author":"Chuzi","year":"2017","journal-title":"Leuk. Lymphoma"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"599","DOI":"10.1016\/j.mayocp.2018.08.022","article-title":"3023 Mayo Clinic Patients with Myeloproliferative Neoplasms: Risk-Stratified Comparison of Survival and Outcomes Data Among Disease Subgroups","volume":"94","author":"Szuber","year":"2019","journal-title":"Mayo Clin. Proc."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"685","DOI":"10.7326\/0003-4819-48-3-685","article-title":"Essential thrombocythemia","volume":"48","author":"Kupfer","year":"1958","journal-title":"Ann. Intern. Med."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"372","DOI":"10.1182\/blood.V6.4.372.372","article-title":"Some Speculations on the Myeloproliferative Syndromes","volume":"6","author":"Dameshek","year":"1951","journal-title":"Blood"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"549","DOI":"10.1002\/1097-0142(19900801)66:3<549::AID-CNCR2820660324>3.0.CO;2-6","article-title":"Clinical course of essential thrombocythemia in 147 cases","volume":"66","author":"Fenaux","year":"1990","journal-title":"Cancer"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"200","DOI":"10.1007\/s12185-019-02800-0","article-title":"The role of calreticulin mutations in myeloproliferative neoplasms","volume":"111","author":"Araki","year":"2020","journal-title":"Int. J. Hematol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"4767","DOI":"10.1007\/s11033-020-05536-x","article-title":"Essential thrombocythemia: A hemostatic view of thrombogenic risk factors and prognosis","volume":"47","author":"Maleknia","year":"2020","journal-title":"Mol. Biol. Rep."},{"key":"ref_9","first-page":"76","article-title":"A review of essential thrombocythemia and its complications","volume":"21","author":"Babakhanlou","year":"2023","journal-title":"Clin. Adv. Hematol. Oncol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"945","DOI":"10.3324\/haematol.2014.106013","article-title":"Optimal therapy for polycythemia vera and essential thrombocythemia can only be determined by the completion of randomized clinical trials","volume":"99","author":"Mascarenhas","year":"2014","journal-title":"Haematologica"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"e38","DOI":"10.1016\/S2352-3026(21)00343-4","article-title":"Symptom burden and quality of life in patients with high-risk essential thrombocythaemia and polycythaemia vera receiving hydroxyurea or pegylated interferon alfa-2a: A post-hoc analysis of the MPN-RC 111 and 112 trials","volume":"9","author":"Mazza","year":"2022","journal-title":"Lancet Haematol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"1144","DOI":"10.1038\/nature03546","article-title":"A unique clonal JAK2 mutation leading to constitutive signalling causes polycythaemia vera","volume":"434","author":"James","year":"2005","journal-title":"Nature"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"2213","DOI":"10.1084\/jem.20131371","article-title":"Myeloproliferative neoplasms can be initiated from a single hematopoietic stem cell expressing JAK2-V617F","volume":"211","author":"Lundberg","year":"2014","journal-title":"J. Exp. Med."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"1062","DOI":"10.1182\/blood-2014-05-578435","article-title":"Clinical effect of driver mutations of JAK2, CALR, or MPL in primary myelofibrosis","volume":"124","author":"Rumi","year":"2014","journal-title":"Blood"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"1599","DOI":"10.1002\/ajh.26008","article-title":"Polycythemia vera and essential thrombocythemia: 2021 update on diagnosis, risk-stratification and management","volume":"95","author":"Tefferi","year":"2020","journal-title":"Am. J. Hematol."},{"key":"ref_16","doi-asserted-by":"crossref","unstructured":"Pikman, Y., Lee, B.H., Mercher, T., McDowell, E., Ebert, B.L., Gozo, M., Cuker, A., Wernig, G., Moore, S., and Galinsky, I. (2006). MPLW515L Is a Novel Somatic Activating Mutation in Myelofibrosis with Myeloid Metaplasia. PLoS Med., 3.","DOI":"10.1371\/journal.pmed.0030270"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"121","DOI":"10.1038\/s41408-018-0159-3","article-title":"MPL-mutated essential thrombocythemia: A morphologic reappraisal","volume":"8","author":"Szuber","year":"2018","journal-title":"Blood Cancer J."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"163","DOI":"10.1016\/bs.ircmb.2021.09.003","article-title":"The mpl mutation","volume":"365","author":"Guglielmelli","year":"2021","journal-title":"Int. Rev. Cell Mol. Biol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"2379","DOI":"10.1056\/NEJMoa1311347","article-title":"Somatic Mutations of Calreticulin in Myeloproliferative Neoplasms","volume":"369","author":"Klampfl","year":"2013","journal-title":"N. Engl. J. Med."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"2391","DOI":"10.1056\/NEJMoa1312542","article-title":"Somatic CALR mutations in myeloproliferative neoplasms with nonmutated JAK2","volume":"369","author":"Nangalia","year":"2013","journal-title":"N. Engl. J. Med."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"281","DOI":"10.1042\/bj3440281","article-title":"Calreticulin: One protein, one gene, many functions","volume":"344","author":"Michalak","year":"1999","journal-title":"Biochem. J."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"8883","DOI":"10.1016\/S0021-9258(19)84464-2","article-title":"Conformational changes induced by binding of divalent cations to calregulin","volume":"261","author":"Khanna","year":"1986","journal-title":"J. Biol. Chem."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"245","DOI":"10.1042\/bj2420245","article-title":"Comparison of calregulins from vertebrate livers","volume":"242","author":"Khanna","year":"1987","journal-title":"Biochem. J."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"36","DOI":"10.1016\/0076-6879(87)39073-1","article-title":"Calregulin: Purification, cellular localization, and tissue distribution","volume":"139","author":"Khanna","year":"1987","journal-title":"Methods Enzymol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"651","DOI":"10.1042\/BJ20081847","article-title":"Calreticulin, a multi-process calcium-buffering chaperone of the endoplasmic reticulum","volume":"417","author":"Michalak","year":"2009","journal-title":"Biochem. J."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1016\/j.it.2012.08.002","article-title":"Calreticulin in the immune system: Ins and outs","volume":"34","author":"Raghavan","year":"2013","journal-title":"Trends Immunol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"157","DOI":"10.1016\/j.ceb.2010.10.011","article-title":"Participation of lectin chaperones and thiol oxidoreductases in protein folding within the endoplasmic reticulum","volume":"23","author":"Rutkevich","year":"2011","journal-title":"Curr. Opin. Cell Biol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"1223","DOI":"10.1016\/j.biocel.2013.03.017","article-title":"Calreticulin-dimerization induced by post-translational arginylation is critical for stress granules scaffolding","volume":"45","author":"Carpio","year":"2013","journal-title":"Int. J. Biochem. Cell Biol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"4741","DOI":"10.1074\/jbc.270.9.4741","article-title":"Calreticulin Functions as a Molecular Chaperone in the Biosynthesis of Myeloperoxidase","volume":"270","author":"Nauseef","year":"1995","journal-title":"J. Biol. Chem."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"20298","DOI":"10.1074\/jbc.270.35.20298","article-title":"Chaperone Function of Calreticulin When Expressed in the Endoplasmic Reticulum as the Membrane-anchored and Soluble Forms","volume":"270","author":"Wada","year":"1995","journal-title":"J. Biol. Chem."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"21458","DOI":"10.1016\/S0021-9258(18)54661-5","article-title":"Expression of calreticulin in Escherichia coli and identification of its Ca2+ binding domains","volume":"266","author":"Baksh","year":"1991","journal-title":"J. Biol. Chem."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"961","DOI":"10.1083\/jcb.200102073","article-title":"Functional specialization of calreticulin domains","volume":"154","author":"Nakamura","year":"2001","journal-title":"J. Cell Biol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"8771","DOI":"10.1074\/jbc.M110.169193","article-title":"Calreticulin Is a Thermostable Protein with Distinct Structural Responses to Different Divalent Cation Environments","volume":"286","author":"Wijeyesakere","year":"2011","journal-title":"J. Biol. Chem."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"3133","DOI":"10.1073\/pnas.051630098","article-title":"Nmr structure of the calreticulin p-domain","volume":"98","author":"Ellgaard","year":"2001","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"525","DOI":"10.1038\/nature24627","article-title":"Structure of the human MHC-I peptide-loading complex","volume":"551","author":"Blees","year":"2017","journal-title":"Nature"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"179","DOI":"10.1016\/bs.ircmb.2021.05.005","article-title":"Calreticulin mutations in myeloproliferative neoplasms","volume":"365","author":"Shide","year":"2021","journal-title":"Int. Rev. Cell Mol. Biol."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"53","DOI":"10.1016\/j.exphem.2017.02.001","article-title":"The Calreticulin control of human stress erythropoiesis is impaired by JAK2V617F in polycythemia vera","volume":"50","author":"Falchi","year":"2017","journal-title":"Exp. Hematol."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"1617","DOI":"10.1080\/07391102.2017.1330224","article-title":"Dissecting physical structure of calreticulin, an intrinsically disordered ca2+-buffering chaperone from endoplasmic reticulum","volume":"36","author":"Migliaccio","year":"2018","journal-title":"J. Biomol. Struct. Dyn."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"5","DOI":"10.1038\/s41422-020-0383-9","article-title":"Calreticulin and cancer","volume":"31","author":"Fucikova","year":"2021","journal-title":"Cell Res."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"2242","DOI":"10.1182\/blood.2019000622","article-title":"Mutant calreticulin in myeloproliferative neoplasms","volume":"134","author":"How","year":"2019","journal-title":"Blood"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"249","DOI":"10.1038\/leu.2014.270","article-title":"Differential association of calreticulin type 1 and type 2 mutations with myelofibrosis and essential thrombocytemia: Relevance for disease evolution","volume":"29","author":"Cabagnols","year":"2015","journal-title":"Leukemia"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"431","DOI":"10.1038\/leu.2015.277","article-title":"Differential clinical effects of different mutation subtypes in CALR-mutant myeloproliferative neoplasms","volume":"30","author":"Pietra","year":"2016","journal-title":"Leukemia"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"371","DOI":"10.1111\/ejh.13561","article-title":"The risk of thrombosis in essential thrombocythemia is associated with the type of CALR mutation: A multicentre collaborative study","volume":"106","author":"Sobas","year":"2021","journal-title":"Eur. J. Haematol."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"935","DOI":"10.1111\/bjh.16276","article-title":"Sequential mutational evaluation of CALR-mutated myeloproliferative neoplasms with thrombocytosis reveals an association between CALR allele burden evolution and disease progression","volume":"188","author":"Cottin","year":"2020","journal-title":"Br. J. Haematol."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"17562864221092093","DOI":"10.1177\/17562864221092093","article-title":"Essential thrombocythemia with CALR mutation and recurrent stroke: Two case reports and literature review","volume":"15","author":"Chen","year":"2022","journal-title":"Ther. Adv. Neurol. Disord."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"2291","DOI":"10.1002\/ccr3.1857","article-title":"Splenic mass in a case of CALR -mutated essential thrombocythemia","volume":"6","author":"Imashuku","year":"2018","journal-title":"Clin. Case Rep."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"157","DOI":"10.1080\/09537104.2020.1869712","article-title":"CALR-ETdb, the database of calreticulin variants diversity in essential thrombocythemia","volume":"33","author":"Cretin","year":"2022","journal-title":"Platelets"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"D941","DOI":"10.1093\/nar\/gky1015","article-title":"COSMIC: The Catalogue of Somatic Mutations in Cancer","volume":"47","author":"Tate","year":"2019","journal-title":"Nucleic Acids Res."},{"key":"ref_49","first-page":"1072","article-title":"Development of myeloproliferative neoplasms by mutant calreticulin: Underlying mechanisms","volume":"59","author":"Araki","year":"2018","journal-title":"Rinsho Ketsueki"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"122","DOI":"10.1038\/s41375-018-0181-2","article-title":"Homomultimerization of mutant calreticulin is a prerequisite for MPL binding and activation","volume":"33","author":"Araki","year":"2019","journal-title":"Leukemia"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"3141","DOI":"10.1111\/jcmm.13413","article-title":"Endoplasmic reticulum in health and disease: The 12th International Calreticulin Workshop, Delphi, Greece","volume":"21","author":"Charonis","year":"2017","journal-title":"J. Cell. Mol. Med."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"e202009179","DOI":"10.1083\/jcb.202009179","article-title":"Mechanism of mutant calreticulin-mediated activation of the thrombopoietin receptor in cancers","volume":"220","author":"Venkatesan","year":"2021","journal-title":"J. Cell Biol."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"S335","DOI":"10.1016\/S2152-2650(20)31001-6","article-title":"MPN-274: Mpl is Activated by Dimers of MPN-Linked Calreticulin Mutants Stabilized by Disulfide Bonds and Ionic Interactions","volume":"20","author":"Venkatesan","year":"2020","journal-title":"Clin. Lymphoma Myeloma Leuk."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"D506","DOI":"10.1093\/nar\/gky1049","article-title":"Uniprot: A worldwide hub of protein knowledge","volume":"47","author":"Consortium","year":"2019","journal-title":"Nucleic Acids Res."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"3389","DOI":"10.1093\/nar\/25.17.3389","article-title":"Gapped BLAST and PSI-BLAST: A new generation of protein database search programs","volume":"25","author":"Altschul","year":"1997","journal-title":"Nucleic Acids Res."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"899","DOI":"10.1107\/S0907444902003451","article-title":"The protein data bank","volume":"58","author":"Berman","year":"2002","journal-title":"Acta Crystallogr. D Biol. Crystallogr."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"408","DOI":"10.1107\/S2052252516012847","article-title":"Structures of parasite calreticulins provide insights into their flexibility and dual carbohydrate\/peptide-binding properties","volume":"3","author":"Moreau","year":"2016","journal-title":"IUCrJ"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"779","DOI":"10.1006\/jmbi.1993.1626","article-title":"Comparative Protein Modelling by Satisfaction of Spatial Restraints","volume":"234","author":"Blundell","year":"1993","journal-title":"J. Mol. Biol."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"2507","DOI":"10.1110\/ps.062416606","article-title":"Statistical potential for assessment and prediction of protein structures","volume":"15","author":"Shen","year":"2006","journal-title":"Protein Sci."},{"key":"ref_60","unstructured":"DeLano, W.L. (2002). PyMOL, Delano Scientific."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1038\/nmeth.3213","article-title":"The I-TASSER Suite: Protein structure and function prediction","volume":"12","author":"Yang","year":"2015","journal-title":"Nat. Methods"},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"1735","DOI":"10.1016\/j.str.2013.08.005","article-title":"High-Resolution Comparative Modeling with RosettaCM","volume":"21","author":"Song","year":"2013","journal-title":"Structure"},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"583","DOI":"10.1038\/s41586-021-03819-2","article-title":"Highly accurate protein structure prediction with AlphaFold","volume":"596","author":"Jumper","year":"2021","journal-title":"Nature"},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"845","DOI":"10.1038\/nprot.2015.053","article-title":"The Phyre2 web portal for protein modeling, prediction and analysis","volume":"10","author":"Kelley","year":"2015","journal-title":"Nat. Protoc."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"1701","DOI":"10.1002\/jcc.20291","article-title":"Gromacs: Fast, flexible, and free","volume":"26","author":"Lindahl","year":"2005","journal-title":"J. Comput. Chem."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"2135","DOI":"10.1002\/jcc.23354","article-title":"Charmm36 all-atom additive protein force field: Validation based on comparison to NMR data","volume":"34","author":"Huang","year":"2013","journal-title":"J. Comput. Chem."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"8001","DOI":"10.1038\/s41598-017-08408-w","article-title":"In silico analysis of glanzmann variants of Calf-1 domain of \u03b1(iib)\u03b2(3) integrin revealed dynamic allosteric effect","volume":"7","author":"Goguet","year":"2017","journal-title":"Sci. Rep."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"2988","DOI":"10.1080\/07391102.2019.1650112","article-title":"Discrete analyses of protein dynamics","volume":"38","author":"Narwani","year":"2020","journal-title":"J. Biomol. Struct. Dyn."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"e4013","DOI":"10.7717\/peerj.4013","article-title":"PBxplore: A tool to analyze local protein structure and deformability with Protein Blocks","volume":"5","author":"Barnoud","year":"2017","journal-title":"PeerJ"},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"2319","DOI":"10.1002\/jcc.21787","article-title":"MDAnalysis: A toolkit for the analysis of molecular dynamics simulations","volume":"32","author":"Denning","year":"2011","journal-title":"J. Comput. Chem."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"271","DOI":"10.1002\/1097-0134(20001115)41:3<271::AID-PROT10>3.0.CO;2-Z","article-title":"Bayesian probabilistic approach for predicting backbone structures in terms of protein blocks","volume":"41","author":"Etchebest","year":"2000","journal-title":"Proteins Struct. Funct. Bioinform."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"137","DOI":"10.1007\/s12551-010-0036-1","article-title":"A short survey on protein blocks","volume":"2","author":"Joseph","year":"2010","journal-title":"Biophys. Rev."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"2025","DOI":"10.1016\/j.biochi.2012.05.028","article-title":"Progressive structure-based alignment of homologous proteins: Adopting sequence comparison strategies","volume":"94","author":"Joseph","year":"2012","journal-title":"Biochimie"},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"20","DOI":"10.3389\/fmolb.2015.00020","article-title":"Protein flexibility in the light of structural alphabets","volume":"2","author":"Craveur","year":"2015","journal-title":"Front. Mol. Biosci."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"21522","DOI":"10.1016\/S0021-9258(20)88216-7","article-title":"Molecular cloning of the high affinity calcium-binding protein (calreticulin) of skeletal muscle sarcoplasmic reticulum","volume":"264","author":"Fliegel","year":"1989","journal-title":"J. Biol. Chem."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"195","DOI":"10.1006\/jmbi.1999.3091","article-title":"Protein secondary structure prediction based on position-specific scoring matrices","volume":"292","author":"Jones","year":"1999","journal-title":"J. Mol. Biol."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"107464","DOI":"10.1016\/j.jsb.2020.107464","article-title":"A structural entropy index to analyse local conformations in intrinsically disordered proteins","volume":"210","author":"Akhila","year":"2020","journal-title":"J. Struct. Biol."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"778","DOI":"10.1002\/prot.22488","article-title":"Improved prediction of protein side-chain conformations with SCWRL4","volume":"77","author":"Krivov","year":"2009","journal-title":"Proteins"},{"key":"ref_79","first-page":"baac005","article-title":"DSDBASE 2.0: Updated version of Disulphide dataBASE, a database on disulphide bonds in proteins","volume":"2022","author":"Kalmankar","year":"2022","journal-title":"Database J. Biol. Databases Curation"},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"95","DOI":"10.1093\/protein\/3.2.95","article-title":"Stereochemical modeling of disulfide bridges. Criteria for introduction into proteins by site-directed mutagenesis","volume":"3","author":"Sowdhamini","year":"1989","journal-title":"Protein Eng. Des. Sel."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"e645","DOI":"10.1016\/j.clml.2020.05.011","article-title":"JAK2, CALR, and MPL Mutations in Egyptian Patients with Classic Philadelphia-negative Myeloproliferative Neoplasms","volume":"20","author":"Soliman","year":"2020","journal-title":"Clin. Lymphoma Myeloma Leuk."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"e333","DOI":"10.1097\/HS9.0000000000000333","article-title":"Mutant Calreticulin in the Myeloproliferative Neoplasms","volume":"4","author":"Prins","year":"2020","journal-title":"Hemasphere"},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"145","DOI":"10.1007\/978-3-030-67696-4_7","article-title":"Roles of calreticulin in protein folding, immunity, calcium signaling and cell transformation","volume":"59","author":"Venkatesan","year":"2021","journal-title":"Prog. Mol. Subcell. Biol."},{"key":"ref_84","doi-asserted-by":"crossref","unstructured":"De Brevern, A.G. (2020). Analysis of protein disorder predictions in the light of a protein structural alphabet. Biomolecules, 10.","DOI":"10.3390\/biom10071080"},{"key":"ref_85","doi-asserted-by":"crossref","unstructured":"Chouquet, A., Pa\u00efdassi, H., Ling, W.L., Frachet, P., Houen, G., Arlaud, G.J., and Gaboriaud, C. (2011). X-ray structure of the human calreticulin globular domain reveals a peptide-binding area and suggests a multi-molecular mechanism. PLoS ONE, 16.","DOI":"10.1371\/journal.pone.0017886"},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"W402","DOI":"10.1093\/nar\/gkz297","article-title":"The PSIPRED Protein Analysis Workbench: 20 years on","volume":"47","author":"Buchan","year":"2019","journal-title":"Nucleic Acids Res."},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"235","DOI":"10.1093\/nar\/28.1.235","article-title":"The protein data bank","volume":"28","author":"Berman","year":"2000","journal-title":"Nucleic Acids Res."},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"679","DOI":"10.1038\/s41592-022-01488-1","article-title":"ColabFold: Making protein folding accessible to all","volume":"19","author":"Mirdita","year":"2022","journal-title":"Nat. Methods"},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"96","DOI":"10.3389\/fcell.2017.00096","article-title":"Calreticulin: Challenges Posed by the Intrinsically Disordered Nature of Calreticulin to the Study of Its Function","volume":"5","author":"Varricchio","year":"2017","journal-title":"Front. Cell Dev. Biol."},{"key":"ref_90","first-page":"e33612","article-title":"Myocardial Infarction as an Initial Presentation of Essential Thrombocythemia with Calreticulin (CALR) Mutation (None Type 1, None Type 2)","volume":"15","author":"Afana","year":"2023","journal-title":"Cureus"},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"21","DOI":"10.1038\/s41408-023-00786-x","article-title":"Phenotypic correlations of CALR mutation variant allele frequency in patients with myelofibrosis","volume":"13","author":"Guglielmelli","year":"2023","journal-title":"Blood Cancer J."},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"e52904","DOI":"10.15252\/embr.202152904","article-title":"Targeting human CALR-mutated MPN progenitors with a neoepitope-directed monoclonal antibody","volume":"23","author":"Tvorogov","year":"2022","journal-title":"EMBO Rep."}],"container-title":["Biomolecules"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2218-273X\/13\/3\/509\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T18:51:55Z","timestamp":1760122315000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2218-273X\/13\/3\/509"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,3,10]]},"references-count":92,"journal-issue":{"issue":"3","published-online":{"date-parts":[[2023,3]]}},"alternative-id":["biom13030509"],"URL":"https:\/\/doi.org\/10.3390\/biom13030509","relation":{},"ISSN":["2218-273X"],"issn-type":[{"value":"2218-273X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,3,10]]}}}