Objective: To probe the function and structure of human selenoprotein P (SELP).
Methods: Several bioinformatic server are used to analyze exons, hydrophobic nature, transmembrane helices and the bonding state of cysteines respectively, as well as the secondary structure and relative solvent accessibility. The homology analysis and searching for motifs or domains in SELP are also carried out.
Results: Two transmembrane helices are found, as is consistent with the hydrophobic nature of SELP. Matured SELP consists of four modules: M1 (Glu20-Ser67/Lys68), M2 (Ser67/Lys68-Asp138/Arg139), M3(Asp138/Arg139-Thr178), M4 (Thr179-Asn381). A coiled coil exists in the second module whose regular secondary structure is higher than that of other three. The percentage of loop structure is higher in the first, third and fourth modules, so they may be three reactive center. The fourth module is the most active one which has a histidine-rich region (His204-His257) on the surface of SELP. Because most of the residues are the E type of solvent accessibility, SELP appears not to be globular. SELP consists of two kinds of domain, so it more probably has more than one function. HUNB_SCAAL, ZP12_BRARE, BR11_BRARE, BRN1_HUMAN which play roles in the development of brain are found have sequence similarity with SELP and the similarity may be the specificity to brain. Other two similar proteins are KNOB_PLAFG and HPN_ HELPY which anchor host thrombospondin or a parasite analog in a binding complex with the endothelial cell receptor and strongly binds nickel and zinc respectively.
Conclusion: The results showed suggest that SELP may have metal binding and endothelial cell membrane anchoring activity which are backed up not only by homology analysis but also the prediction of structure. Moreover, the results also suggest the specificity of SELP to brain.