|
Figure 4.
Mechanism of the actin cytoskeleton disruption by MARTX[Vc].
Upon transport through the cytoplasmic membrane of the host
cell, the cysteine protease domain (CPD) of MARTX[Vc] cleaves
and releases into the cytoplasm functional domains, the
Rho-inactivation domain (RID) and the actin cross-linking domain
(ACD). RID shifts equilibrium from F- to G-actin by affecting
Rho signaling via an unknown mechanism. ACD uses the enriched
G-actin pool, maintained by thymosin β4 and profilin, as a
substrate for covalent cross-linking dependent on the hydrolysis
of ATP. In the resulting oligomers of actin, residue K50 of each
actin protomer is connected via an iso-peptide bond with E270 of
an adjacent protomer in a conformation incompatible with
polymerization. This results in irreversible disruption of the
actin cytoskeleton. The white background highlights the
mechanism of action elucidated for ACD in the present study.
|
