5hca
Globular Domain of the Entamoeba histolytica calreticulin in complex with glucose
Structural highlights
FunctionCALR_ENTH1 Molecular calcium-binding chaperone promoting folding, oligomeric assembly and quality control in the ER via the calreticulin/calnexin cycle (By similarity). This lectin may interact transiently with almost all of the monoglucosylated glycoproteins that are synthesized in the ER (By similarity). Plays a role in host cell phagocytosis, possibly by acting as a receptor for host C1q (PubMed:22473608). Binding to C1q prevents the activation of the host classical complement pathway (PubMed:24860808). Also, binds to apoptotic host cells independently of host C1q and collectins (PubMed:22473608).[UniProtKB:P27797][1] [2] Publication Abstract from PubMedCalreticulin (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. Structures of parasite calreticulins provide insights into their flexibility and dual carbohydrate/peptide-binding properties.,Moreau C, Cioci G, Iannello M, Laffly E, Chouquet A, Ferreira A, Thielens NM, Gaboriaud C IUCrJ. 2016 Sep 14;3(Pt 6):408-419. eCollection 2016 Nov 1. PMID:27840680[3] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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