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shares an overall topology with the fibronectin type III fold. The D1/D2
domains are almost perpendicular to one another and form an inverted “L”
with the ligand-binding site located between the monomers. Consistent with
the cytokine family of receptors, the EPOR has a WSXWS box that is a
sequence of amino acids containing tryptophan and serine that are essential for
the biologic activity of the receptor [17].
In addition to the predominantly
-helix is found at the
amino terminus, which may have important structural implications (Fig. 3).
Adopting the position inside the “elbow” of the D1 and D2 domains, the
α
-sheet structure, an
β
α
-helix makes extensive contacts with both D1 and D2 domains of the recep-
tor, with buried surface area of approximately 200 Å 2 . The
-helix is amphi-
pathic, having both hydrophobic and hydrophilic regions, and presents several
residues towards a hydrophobic patch on the D1 domain of the receptor. Phe11
and Leu18 of the
α
-helix form the basis of hydrophobic interactions with
Phe39, Leu27, and Phe29 in the D1 domain. N -terminal to the WSXWS box
N
α
Figure 3. Amino acid contacts of amino terminal
-helix of EPOR. Ribbon representation of the sol-
uble EPOR. Selected residues at the helical interface are depicted using a stick model. Residues 209
to 212 represent the putative cytokine family WSXWS box. The EPOR N -terminal
α
N α-helix is amphi-
pathic and presents several hydrophobic residues towards a hydrophobic patch on the D1 domain of
the receptor. Phe11 and Leu18 of the
-helix form the basis of the hydrophobic interactions with
Phe39, Leu27, and Phe29 in the D1 domain. N -terminal to the WSXWS box on domain D2, Phe208
N
also makes contacts with this hydrophobic pocket. Two electrostatic interactions occur between the
α-helix and the rest of the protein. One salt bridge is formed between Glu12 and Arg80, and the other
salt bridge links all three domains by the electrostatic interactions of Lys14 with Glu31 (on domain
D1) and Asp122 (on domain D2).
α
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