Figure 1

The simulation-derived JH1/JH2 interface of JAK2. Upper: The overall relative positions of JH1 and JH2. JH1 and JH2 form an anti-symmetrical pair (dimer). The N- and C- lobes of JH1 and JH2 are shown in different colors and are indicated by text with the corresponding color. The circled area is the main region of the JH1/JH2 interface relevant to JAK2 auto-regulation. The red loop is part of the JH1 activation loop (residues 995 to 1005). Lower: A more detailed view of the JH1/JH2 interface. The curved arrow indicates the torsion angle between the C-helices of JH1 and JH2. The blue labels (I-1, I-2, and I-3) indicate the sub-interfaces, or groups of interactions, defined in the previous work[42]: I-1, interactions between the C-helices of JH1 and JH2; I-2, interactions between the JH1 activation loop and the JH2 C-helix; and I-3, interactions between the JH1 activation loop and residues near position 617 of JH2.