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Figure 1.
Fig. 1. Comparison of the unliganded and liganded EPOR
receptor dimer configurations. (A) A schematic representation of
the quaternary structure of the native EBP dimer. The two EBP
molecules form a cross-like self dimer and are shown in cyan and
gold, with their individual domains labeled D1 and D2. A close,
symmetrical interaction is formed between the two EBP molecules
on the basis of their previously determined ligand-binding
epitope regions (11). The three-residue linker between the
NH[2]-terminal  helix and
the FBN-III domains in both molecules is omitted because of the
lack of electron density in this region and the NH[2]-terminal
helices
are omitted for clarity. The D1 domains of each monomer point in
opposite directions, whereas the two D2 domains can both be
aligned toward the membrane with a rotation of 135° between
them. The membrane-proximal ends of D2 in each molecule (Thr220)
are shown by a black arrow emphasizing the 73 Å separation
between them. In the schematic of the unliganded self dimer
(right), the different scissors-like dimer configuration keeps
the intracellular ends far enough apart such that
autophosphorylation of JAK-2 cannot occur and hence other
phosphorylation events, such as on the cytoplasmic domain of the
EPOR, do not occur. (B) The quaternary structure of the EBP-EMP1
complex. The two EBP molecules are shown in gold and cyan and
the EMP1 dimer in purple. Two EMP1 peptides bind to two EBP
receptor molecules in a symmetrical manner (11). The domains are
labeled in D1 and D2 and the equivalent COOH-terminal
membrane-proximal ends of each receptor are shown by black
arrows that highlight the difference in distances and receptor
dimer configurations for the unliganded native and
EMP1-complexed EBPs. In the schematic of the liganded form
(right), EMP1 [or EPO (13)] induces a close dimer association of
both the D1 and D2 domains so that their intracellular regions
become substrates for phosphorylation by two JAK-2 molecules.
The stick figures were made with MIDAS (30).
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