Amino acid residues of huEPO and huEPOR that contact each other in site 1 and site 2 intermolecular contact areas, and the corresponding residues in <i>xl</i>EPO.

<p>^<i>a</i><i>xl</i>EPO residues corresponding to right-hand “huEPO residues” [<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0124676#pone.0124676.ref021" target="_blank">21</a>]. Amino acid residues that are identical to huEPO residues are in bold.</p><p>^<i>b</i>Buried residues (>5.0 Ų) of huEPO in site 1 and site 2 intermolecular contact areas [<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0124676#pone.0124676.ref030" target="_blank">30</a>]. Available mutagenesis information [<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0124676#pone.0124676.ref026" target="_blank">26</a>–<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0124676#pone.0124676.ref029" target="_blank">29</a>] are highlighted according to the maximal degree of loss of <i>in vitro</i> bioactivity: bold underlined, >50-fold; bold, >5-fold; underlined, 2–5-fold; not highlighted, no effect.</p><p>^<i>c</i>HuEPOR residues within 4.5-Å distance from huEPO in the crystal structure of human EPO-(EPOR)₂ complex (Protein Data Bank accession number, 1EER) [<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0124676#pone.0124676.ref030" target="_blank">30</a>]. Amino acid residues that are conserved in <i>X</i>. <i>laevis</i> are in bold [<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0124676#pone.0124676.ref049" target="_blank">49</a>].</p><p>^<i>d</i>Amino acid residues of huEPO and huEPOR that form interactions with each other, such as hydrogen bond and hydrophobic binding, are in italics [<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0124676#pone.0124676.ref030" target="_blank">30</a>].</p><p>^<i>e</i>Amino acid residues of <i>xl</i>EPOR that conserved in huEPOR[<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0124676#pone.0124676.ref049" target="_blank">49</a>].</p><p>huEPO, human erythropoietin; huEPOR, human EPO receptor; <i>xl</i>EPO, <i>X</i>. <i>laevis</i> EPO.</p><p>Amino acid residues of huEPO and huEPOR that contact each other in site 1 and site 2 intermolecular contact areas, and the corresponding residues in <i>xl</i>EPO.