title: The folded and disordered domains of human ribosomal protein SA have both idiosyncratic and shared functions as membrane receptors.
abstract: The human RPSA [ribosomal protein SA; also known as LamR1(laminin receptor 1)] belongs to the ribosome but is also a membrane receptor for laminin, growth factors, prion, pathogens and the anticarcinogen EGCG (epigallocatechin-gallate). It contributes to the crossing of the blood-brain barrier by neurotropic viruses and bacteria, and is a biomarker of metastasis. RPSA includes an N-terminal domain, which is folded and homologous to the prokaryotic RPS2, and a C-terminal extension, which is intrinsically disordered and conserved in vertebrates. We used recombinant derivatives of RPSA and its N- and C-domains to quantify its interactions with ligands by in-vitro immunochemical and spectrofluorimetric methods. Both N- and C-domains bound laminin with K(D) (dissociation constants) of 300 nM. Heparin bound only to the N-domain and competed for binding to laminin with the negatively charged C-domain, which therefore mimicked heparin. EGCG bound only to the N-domain with a K(D) of 100 nM. Domain 3 of the envelope protein from yellow fever virus and serotypes-1 and -2 of dengue virus bound preferentially to the C-domain whereas that from West Nile virus bound only to the N-domain. Our quantitative in-vitro approach should help clarify the mechanisms of action of RPSA, and ultimately fight against cancer and infectious agents.
authors.affiliation: Institut Pasteur, Unit of Molecular Prevention and Therapy of Human Diseases, Department of Infection and Epidemiology, rue du Dr. Roux, F-75015 Paris, France.
authors.forename: Nora
authors.initials: N
authors.lastname: Zidane
authors.forename: Mohamed B
authors.initials: MB
authors.lastname: Ould-Abeih
authors.forename: Isabelle
authors.initials: I
authors.lastname: Petit-Topin
authors.forename: Hugues
authors.initials: H
authors.lastname: Bedouelle
mesh_terms: D002462:Cell Membrane / Q000378:metabolism*; D004797:Enzyme-Linked Immunosorbent Assay; D004926:Escherichia coli / Q000235:genetics / Q000378:metabolism; D006493:Heparin / Q000378:metabolism; D006801:Humans; D007120:Immunochemistry; D007797:Laminin / Q000378:metabolism; D008024:Ligands; D011485:Protein Binding; D017510:Protein Folding; D025941:Protein Interaction Mapping / Q000379:methods*; D017434:Protein Structure, Tertiary; D017474:Receptors, Laminin / Q000235:genetics / Q000378:metabolism*; D011994:Recombinant Proteins / Q000235:genetics / Q000378:metabolism; D012269:Ribosomal Proteins / Q000235:genetics / Q000378:metabolism*; D013050:Spectrometry, Fluorescence / Q000379:methods; D014364:Tryptophan / Q000378:metabolism; D014759:Viral Envelope Proteins / Q000378:metabolism; D014902:West Nile virus / Q000378:metabolism; D015005:Yellow fever virus / Q000378:metabolism
chemical_list: D007797:Laminin; D008024:Ligands; C510624:RPSA protein, human; D017474:Receptors, Laminin; D011994:Recombinant Proteins; D012269:Ribosomal Proteins; D014759:Viral Envelope Proteins; C065696:glycoprotein E, Flavivirus; D014364:Tryptophan; D006493:Heparin