Atomic basis of the exquisite specificity of phosphate and sulfate transport receptors.
We have determined, by the method of x-ray crystallography, the 1.7 A resolution three-dimensional structures of the ligand-bound form of the phosphate receptor as well as the sulfate receptor. These protein structures provide an unprecedented atomic-level understanding of the mechanism governing the exquisite specificity of each receptor. Although they lack amino acid sequence homology, both receptors have very similar three-dimensional structure. The structure consists of two globular domains separated by a deep cleft which contains the ligand-binding site. The bound phosphate and sulfate are totally devoid of water of hydration. The bound phosphate is tightly held in place by 12 hydrogen bonds, 11 with donor and 1 with acceptor groups. The acceptor group (an Asp carboxylate side chain) plays three key roles. It confers specificity by directly recognizing one proton of either the monobasic or dibasic phosphate. It also assists in the recognition of another proton of the monobasic phosphate. Finally, because of charge repulsion, it disallows binding of fully ionized sulfate. The sulfate bound to the sulfate receptor makes seven hydrogen bonds with uncharged polar groups exclusively. The absence of an acceptor group in the binding site of the sulfate receptor is not conducive to phosphate binding.
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Howard Hughes Medical Institute, Houston, Texas, USA.
D001692:Biological Transport / Q000502:physiology; D018360:Crystallography, X-Ray; D010710:Phosphates / Q000378:metabolism*; D011487:Protein Conformation; D011956:Receptors, Cell Surface / Q000737:chemistry*; D012680:Sensitivity and Specificity; D013431:Sulfates / Q000378:metabolism*
D010710:Phosphates; D011956:Receptors, Cell Surface; D013431:Sulfates