Figure 5
From: A human β-III-spectrin spinocerebellar ataxia type 5 mutation causes high-affinity F-actin binding
Model: Closed and open conformations control binding of the β-III-spectrin ABD to F-actin.
In the closed conformation (top structure, represented by the β-III-spectrin structural homology model) the two CH domains closely associate and this interaction is promoted by leucine 253 and its CH1 domain hydrophobic contacts. In the open conformation (bottom structure, CH1 and CH2 domains of the structural homology model were arbitrarily separated), leucine 253 no longer contacts the CH1 domain and the two CH domains are spatially separated. The closed conformation does not bind actin while the open state favors interaction with actin. The closed and open conformations may exist in equilibrium or the open conformation may correspond to a transition state that occurs in the F-actin binding reaction. The L253P mutation causes the ABD to adopt the open conformation by disrupting CH1-CH2 domain hydrophobic interactions normally mediated by leucine 253.
