Biology Reference
In-Depth Information
Figure 2. A secondary structure depiction of rHuEPO. rHuEPO has a structural topology that is sim-
ilar to other members of the cytokine hormone family. The characteristic topology of EPO, and of
cytokines in general, is a core structure composed of four helices. One pair of anti-parallel long
helices, A (residues 8 to 26), and D (residues 137 to 161), and another pair of short helices, B (residues
56 to 83), and C (residues 90 to 112) complete the helical bundle.
pack against the hydrophobic residues of helices A, B, and C, which reflect the
pattern of the approximate 3.5 residues per turn in a standard
-helix.
In the X-ray structure of rHuEPO bound to EPOR, two additional short
helices are found: the B' helix (residues 47 to 52) orthogonal to B and the
mini-helix C' (residues 114 to 121) following C with a 90° tilt beginning at
Gly113. The second mini-helix is not found in the NMR structure and may be
an artifact of the mutations made in this area to develop a protein suitable for
crystallization.
α
Structure of EPOR
The extracellular domain of the rHuEPO receptor has two
sandwich
β
domains, designated D1 (
N
-terminal) and D2 (
N
C
-terminal), each of which
