5HCA

Globular Domain of the Entamoeba histolytica calreticulin in complex with glucose

Summary for 5HCA

• Entry DOI: 10.2210/pdb5hca/pdb
• Descriptor: Calreticulin,Calreticulin, CALCIUM ION, SULFATE ION, ... (8 entities in total)
• Functional Keywords: chaperone, legume lectin domain, sugar binding protein
• Biological source: Entamoeba histolytica HM-1:IMSS; More
• Total number of polymer chains: 3
• Total formula weight: 95342.28

Authors

Moreau, C.P.,Gaboriaud, C. (deposition date: 2016-01-04, release date: 2016-08-31, Last modification date: 2024-11-06)

Primary citation

Moreau, C.,Cioci, G.,Iannello, M.,Laffly, E.,Chouquet, A.,Ferreira, A.,Thielens, N.M.,Gaboriaud, C.
Structures of parasite calreticulins provide insights into their flexibility and dual carbohydrate/peptide-binding properties.
IUCrJ, 3:408-419, 2016

PubMed Abstract: Calreticulin (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 , , , and . 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 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.

PubMed: 27840680
DOI: 10.1107/S2052252516012847

Experimental method

X-RAY DIFFRACTION (2.15 Å)