title: Peptide binding specificity of the chaperone calreticulin.
abstract: Calreticulin is a molecular chaperone with specificity for polypeptides and N-linked monoglucosylated glycans. In order to determine the specificity of polypeptide binding, the interaction of calreticulin with polypeptides was investigated using synthetic peptides of different length and composition. A large set of available synthetic peptides (n=127) was tested for binding to calreticulin and the results analysed by multivariate data analysis. The parameter that correlated best with binding was hydrophobicity while beta-turn potential disfavoured binding. Only hydrophobic peptides longer than 5 amino acids showed binding and a clear correlation with hydrophobicity was demonstrated for oligomers of different hydrophobic amino acids. Insertion of hydrophilic amino acids in a hydrophobic sequence diminished or abolished binding. In conclusion our results show that calreticulin has a peptide-binding specificity for hydrophobic sequences and delineate the fine specificity of calreticulin for hydrophobic amino acid residues.
authors.affiliation: Department of Autoimmunology, Statens Serum Institut, Artillerivej 5, DK-2300 Copenhagen, Denmark.
authors.forename: Noreen
authors.initials: N
authors.lastname: Sandhu
authors.forename: Karen
authors.initials: K
authors.lastname: Duus
authors.forename: Charlotte S
authors.initials: CS
authors.lastname: Jørgensen
authors.forename: Paul R
authors.initials: PR
authors.lastname: Hansen
authors.forename: Susanne W
authors.initials: SW
authors.lastname: Bruun
authors.forename: Lars Ø
authors.initials: LØ
authors.lastname: Pedersen
authors.forename: Peter
authors.initials: P
authors.lastname: Højrup
authors.forename: Gunnar
authors.initials: G
authors.lastname: Houen
mesh_terms: D000595:Amino Acid Sequence; D000596:Amino Acids / Q000737:chemistry / Q000378:metabolism; D037282:Calreticulin / Q000378:metabolism*; D015395:Histocompatibility Antigens Class I / Q000378:metabolism; D006801:Humans; D057927:Hydrophobic and Hydrophilic Interactions; D018832:Molecular Chaperones / Q000378:metabolism*; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000737:chemistry / Q000378:metabolism*; D011328:Prions / Q000737:chemistry / Q000378:metabolism; D011485:Protein Binding; D012680:Sensitivity and Specificity; D000683:Serum Amyloid P-Component / Q000737:chemistry / Q000378:metabolism
chemical_list: D000596:Amino Acids; D037282:Calreticulin; D015395:Histocompatibility Antigens Class I; D018832:Molecular Chaperones; D010446:Peptide Fragments; D011328:Prions; D000683:Serum Amyloid P-Component