The Influence of Catalysis on Mad2 Activation Dynamics
Figure 1
Chemical Reactions That Control the Activation of the SAC
(A) Ribbon model of O-Mad2 [39]. Ribbon models were obtained with PyMol, by DeLano Scientific (http://www.pymol.org). The invariant core of the structure (N) is shown in red. The C-terminal mobile element (C), known as the “safety belt” [22], is in green.
(B) Ribbon model of C-Mad2. The core of the structure is coloured yellow, with the C-terminal tail and safety belt in green. A segment of Mad1 that stabilizes the C-Mad2 conformation is shown in grey [22].
(C) Ribbon diagram of the O-Mad2:C-Mad2 asymmetric dimer with same colour codes as (A) and (B) [14].
(D) The Mad2 template model [13]. O-Mad2 and C-Mad2 are represented with red squares and yellow circles, respectively. Mad1 is represented with grey cylinders. The Mad2 binding site in Mad1 and Cdc20 is shown as a thin grey cylinder. The light-yellow hexagon includes all the reactions taking place at unattached kinetochores (Un-KT), while the grey hexagon includes cytosolic reactions. Cdc20:C-Mad2 is the only chemical species that belongs to both sets. The reactions describe binding (1), dimerization (2 and 4), and catalysis (3 and 5). An underlying hypothesis of these reactions is the presence of a highly unstable form of active Mad2, I-Mad2, more prone to bind Cdc20 than O-Mad2. For the sake of simplicity, we do not include it explicitly in our reaction scheme. In Table S1, we report the differential equations formalizing the reaction network.
(E) The reactions of dimerization and catalysis form a closed loop that produces the binding reaction. Since no energy is introduced into the system, microscopic reversibility applies, and the hypothetical reaction does not affect the equilibrium of the system.