title: 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 Ca(2+)-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 extend this site by creating a binding cavity lined by hydrophobic residues. These data thus provide a first structural insight into the lectin-independent binding properties of calreticulin and suggest new working hypotheses, including that of a multi-molecular mechanism.
authors.affiliation: Institut de Biologie Structurale Jean-Pierre Ebel, CEA, Grenoble, France.
authors.forename: Anne
authors.initials: A
authors.lastname: Chouquet
authors.forename: Helena
authors.initials: H
authors.lastname: Païdassi
authors.forename: Wai Li
authors.initials: WL
authors.lastname: Ling
authors.forename: Philippe
authors.initials: P
authors.lastname: Frachet
authors.forename: Gunnar
authors.initials: G
authors.lastname: Houen
authors.forename: Gérard J
authors.initials: GJ
authors.lastname: Arlaud
authors.forename: Christine
authors.initials: C
authors.lastname: Gaboriaud
mesh_terms: D000595:Amino Acid Sequence; D001665:Binding Sites; D037282:Calreticulin / Q000737:chemistry* / Q000378:metabolism*; D018360:Crystallography, X-Ray; D006801:Humans; D037102:Lectins / Q000378:metabolism; D008958:Models, Molecular; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000737:chemistry; D010455:Peptides / Q000737:chemistry / Q000378:metabolism*; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D013499:Surface Properties
chemical_list: D037282:Calreticulin; D037102:Lectins; D010446:Peptide Fragments; D010455:Peptides