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Structures of parasite calreticulins provide insights into their flexibility and dual carbohydrate/peptide-binding properties

Authordc.contributor.authorMoreau, Christophe 
Authordc.contributor.authorCioci, Gianluca 
Authordc.contributor.authorIannello, Marina 
Authordc.contributor.authorLaffly, Emmanuelle 
Authordc.contributor.authorChouquet, Anne 
Authordc.contributor.authorFerreira, Arturo 
Authordc.contributor.authorThielens, Nicole M. 
Authordc.contributor.authorGaboriaud, Christine 
Cita de ítemdc.identifier.citationIUCrJ (2016). 3, 408–419es_ES
Abstractdc.description.abstractCalreticulin (CRT) is a multifaceted protein, initially discovered as an endoplasmic reticulum (ER) chaperone protein, that is essential in calcium metabolism. Various implications in cancer, early development and immunology have been discovered more recently for CRT, as well as its role as a dominant 'eat-me' prophagocytic signal. Intriguingly, cell-surface exposure/secretion of CRT is among the infective strategies used by parasites such as Trypanosoma cruzi, Entamoeba histolytica, Taenia solium, Leishmania donovani and Schistosoma mansoni. Because of the inherent flexibility of CRTs, their analysis by X-ray crystallography requires the design of recombinant constructs suitable for crystallization, and thus only the structures of two very similar mammalian CRT lectin domains are known. With the X-ray structures of two distant parasite CRTs, insights into species structural determinants that might be harnessed to fight against the parasites without affecting the functions of the host CRT are now provided. Moreover, although the hypothesis that CRT can exhibit both open and closed conformations has been proposed in relation to its chaperone function, only the open conformation has so far been observed in crystal structures. The first evidence is now provided of a complex conformational transition with the junction reoriented towards P-domain closure. SAXS experiments also provided additional information about the flexibility of T. cruzi CRT in solution, thus complementing crystallographic data on the open conformation. Finally, regarding the conserved lectin-domain structure and chaperone function, evidence is provided of its dual carbohydrate/protein specificity and a new scheme is proposed to interpret such unusual substrate-binding properties. These fascinating features are fully consistent with previous experimental observations, as discussed considering the broad spectrum of CRT sequence conservations and differences.es_ES
Patrocinadordc.description.sponsorshipFrench National Research Agency ANR 09-PIRI-0021 FRISBI ANR-10-INSB-05-02 GRAL within the Grenoble Partnership for Structural Biology (PSB) ANR-10-LABX-49-01es_ES
Publisherdc.publisherInt Union Crystallographyes_ES
Type of licensedc.rightsAttribution-NonCommercial-NoDerivs 3.0 Chile*
Link to Licensedc.rights.uri*
Keywordsdc.subjectProtein structurees_ES
Keywordsdc.subjectMolecular recognitiones_ES
Keywordsdc.subjectX-ray crystallographyes_ES
Keywordsdc.subjectSolution scatteringes_ES
Títulodc.titleStructures of parasite calreticulins provide insights into their flexibility and dual carbohydrate/peptide-binding propertieses_ES
Document typedc.typeArtículo de revistaes_ES
Indexationuchile.indexArtículo de publicación ISIes_ES

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Attribution-NonCommercial-NoDerivs 3.0 Chile
Except where otherwise noted, this item's license is described as Attribution-NonCommercial-NoDerivs 3.0 Chile