2011
DOI: 10.1371/journal.pone.0017886
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X-Ray Structure of the Human Calreticulin Globular Domain Reveals a Peptide-Binding Area and Suggests a Multi-Molecular Mechanism

Abstract: In the endoplasmic reticulum, calreticulin acts as a chaperone and a Ca2+-signalling protein. At the cell surface, it mediates numerous important biological effects. The crystal structure of the human calreticulin globular domain was solved at 1.55 Å resolution. Interactions of the flexible N-terminal extension with the edge of the lectin site are consistently observed, revealing a hitherto unidentified peptide-binding site. A calreticulin molecular zipper, observed in all crystal lattices, could further exten… Show more

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Cited by 90 publications
(125 citation statements)
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“…It turned out that anti-LRP impaired the binding of soluble PR3 to macrophages, thus suggesting (but not demonstrating) that a direct association between PR3 and LRP (or LRP-containing complexes) could occur. It also should be mentioned that CRT is also expressed at the surface of macrophages, and that homotypic CRT-CRT interactions have also been described during the phagocytosis of apoptotic cells (14,22). It thus could be foreseen that PR3-CRT association might interfere with this CRT-CRT homotypic interaction (Fig.…”
Section: Crt-pr3 Association Disables the Lrp-crt-mediated Phagocyticmentioning
confidence: 99%
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“…It turned out that anti-LRP impaired the binding of soluble PR3 to macrophages, thus suggesting (but not demonstrating) that a direct association between PR3 and LRP (or LRP-containing complexes) could occur. It also should be mentioned that CRT is also expressed at the surface of macrophages, and that homotypic CRT-CRT interactions have also been described during the phagocytosis of apoptotic cells (14,22). It thus could be foreseen that PR3-CRT association might interfere with this CRT-CRT homotypic interaction (Fig.…”
Section: Crt-pr3 Association Disables the Lrp-crt-mediated Phagocyticmentioning
confidence: 99%
“…1C). Recombinant CRT, the CRT P domain, and the CRT globular domain designed to preserve the CRT structural domain limits (15,22) were immobilized on a CM5 sensor chip. The kinetic parameters of CRT recognition were determined by recording sensorgrams at varying PR3 concentrations from 10 to 100 nM.…”
Section: Pr3 and Crt Are Colocalized On Neutrophil Membrane On Apoptosismentioning
confidence: 99%
“…the Glycan-binding Site of Calreticulin-Previously, the crystal structure of the globular domain of human calreticulin (Protein Data Bank code 3pos) had suggested the presence of a polypeptide-binding site located on the edge of the lectin-binding site of calreticulin (6). To further examine this possibility, we asked whether occupancy of the glycan-binding site of calreticulin with the calreticulin-specific glycan Glc␣1-3Man␣1-2Man␣1-2Man G1M3 could limit interactions between calreticulin and protein substrates.…”
Section: Identification Of a Polypeptide-binding Site In Proximity Tomentioning
confidence: 99%
“…However, either these mutants were destabilizing (45), or they did not impair aggregation suppression function under physiological conditions of the ER (28). More recently, interest has focused around the lectin binding site because a crystal structure of the Crt globular domain detected an N-terminal affinity tag interacting with the edge of the lectin site (31). Indeed, a mutation at Trp-319 within the lectin site has been reported to attenuate aggregation suppression in vitro (32).…”
Section: Discussionmentioning
confidence: 99%
“…Several protein binding sites have been identified on Crt such as those specific for GABARAP (29) and thrombospondin (30), but interacting peptides derived from these proteins fail to compete in aggregation suppression assays, indicative of distinct binding sites (24). Additional binding sites have been proposed in proximity to the lectin site (22,31,32), but these either do not exhibit the expected specificity for hydrophobic substrates (22) or would be expected to be blocked upon addition of monoglucosylated oligosaccharide (31), a treatment that does not affect the binding of hydrophobic peptides to Crt (24).…”
mentioning
confidence: 99%