Serendipitous discovery and X-ray structure of a human phosphate binding apolipoprotein.
We report the serendipitous discovery of a human plasma phosphate binding protein (HPBP). This 38 kDa protein is copurified with the enzyme paraoxonase. Its X-ray structure 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 systematic absence of complete genes for eukaryotic phosphate-SBP from databases is intriguing, but the astonishing 90% sequence conservation between genes belonging to evolutionary distant species suggests that the corresponding proteins play an important function. HPBP is the only known transporter capable of binding phosphate ions in human plasma and may become a new predictor of or a potential therapeutic agent for phosphate-related diseases such as atherosclerosis.
Laboratoire de Cristallogenèse et Cristallographie des Protéines, Institut de Biologie Structurale JP EBEL, 38027 Grenoble, France.
Renaud
R
Morales
Anne
A
Berna
Philippe
P
Carpentier
Carlos
C
Contreras-Martel
Frédérique
F
Renault
Murielle
M
Nicodeme
Marie-Laure
ML
Chesne-Seck
François
F
Bernier
Jérôme
J
Dupuy
Christine
C
Schaeffer
Hélène
H
Diemer
Alain
A
Van-Dorsselaer
Juan C
JC
Fontecilla-Camps
Patrick
P
Masson
Daniel
D
Rochu
Eric
E
Chabriere
D000595:Amino Acid Sequence; D001053:Apolipoproteins / Q000737:chemistry* / Q000378:metabolism; D043303:Aryldialkylphosphatase / Q000737:chemistry* / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000737:chemistry / Q000235:genetics; D006801:Humans; D008024:Ligands; D008969:Molecular Sequence Data; D028044:Phosphate-Binding Proteins / Q000737:chemistry / Q000378:metabolism; D010710:Phosphates / Q000378:metabolism*; D063150:Polycomb Repressive Complex 1; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D017386:Sequence Homology, Amino Acid; D044767:Ubiquitin-Protein Ligases; D014961:X-Ray Diffraction / Q000379:methods; D014965:X-Rays
D001053:Apolipoproteins; D004268:DNA-Binding Proteins; D008024:Ligands; D028044:Phosphate-Binding Proteins; D010710:Phosphates; D063150:Polycomb Repressive Complex 1; C489841:RNF2 protein, human; D044767:Ubiquitin-Protein Ligases; D043303:Aryldialkylphosphatase; C468406:PON1 protein, human