title: [Discovery and crystallographic structure of human apolipoprotein].
abstract: We report the serendipitous discovery of a human plasma phosphate binding protein (HPBP). This 38 kDa protein is co-purified with paraoxonase (PON1). The association between HPON1 and HPBP is modulated by phosphate and calcium concentrations. The HPBP X-ray structure solved at 1.9 A resolution is similar to the prokaryotic phosphate solute-binding proteins (SBPs) associated with ATP binding cassette transmembrane transporters, though phosphate-SBPs have never been characterized or predicted from nucleic acid databases in eukaryotes. However, HPBP belongs to the family of ubiquitous eukaryotic proteins named DING, meaning that phosphate-SBPs are also widespread in eukaryotes. The absence of complete genes for eukaryotic phosphate-SBP from databases is intriguing, but the astonishing 90% sequence conservation of genes between evolutionary distant species suggests that the corresponding proteins play an important function. HPBP is the first identified transporter capable of binding phosphate ions in human plasma. Thus it is thought to become a new predictor and a potential therapeutic agent for phosphate-related diseases such as atherosclerosis.
authors.affiliation: Laboratoire de cristallogenèse et cristallographie des Protéines, Institut de Biologie Structurale J.-P. Ebel, F 38027 Grenoble.
authors.forename: R
authors.initials: R
authors.lastname: Morales
authors.forename: A
authors.initials: A
authors.lastname: Berna
authors.forename: P
authors.initials: P
authors.lastname: Carpentier
authors.forename: C
authors.initials: C
authors.lastname: Contreras-Martel
authors.forename: F
authors.initials: F
authors.lastname: Renault
authors.forename: M
authors.initials: M
authors.lastname: Nicodeme
authors.forename: M-L
authors.initials: ML
authors.lastname: Chesne-Seck
authors.forename: F
authors.initials: F
authors.lastname: Bernier
authors.forename: J
authors.initials: J
authors.lastname: Dupuy
authors.forename: C
authors.initials: C
authors.lastname: Schaeffer
authors.forename: H
authors.initials: H
authors.lastname: Diemer
authors.forename: A
authors.initials: A
authors.lastname: Van-Dorsselaer
authors.forename: J C
authors.initials: JC
authors.lastname: Fontecilla-Camps
authors.forename: P
authors.initials: P
authors.lastname: Masson
authors.forename: D
authors.initials: D
authors.lastname: Rochu
authors.forename: E
authors.initials: E
authors.lastname: Chabrière
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001053:Apolipoproteins / Q000737:chemistry*; D043303:Aryldialkylphosphatase / Q000737:chemistry; D018360:Crystallography, X-Ray; D006801:Humans; D008958:Models, Molecular; D008969:Molecular Sequence Data; D010710:Phosphates / Q000097:blood
chemical_list: D001053:Apolipoproteins; D010710:Phosphates; D043303:Aryldialkylphosphatase; C468406:PON1 protein, human