ИСТИНА

Native actin, G-actin, is formed in vivo as a result of complex posttranslational folding processes that require the ATP energy expenditure and are assisted by Hsp70, prefoldin, and chaperonin CCT. G-actin is stabilized by binding of one ATP molecule and one Ca2+ ion (or Mg2+ in vivo). Chemical denaturants, heating, or Ca2+ removal transform actin into the ‘inactivated actin’ (I), compact oligomer formed by 14–16 subunits. Viscogenic and crowding agents slow this process down but do not stop it. The lack of calciumin solution accelerates spontaneous transition from globular to inactivated state. Therefore, native G-actin has thermodynamically unstable structure that in the absence of Ca2+ spontaneously converts to the I-state, which is a thermodynamically stable form of this protein. However, kinetically, G-actin represents a stable form due to the high free energy barrier between the G- and inactivated state. Noteworthy, native actin has much in common with intrinsically disordered proteins (IDPs): it has functionally important disordered regions, it is constantly in complex with one of its numerous partners, and it plays key roles in many cellular processes, similar to disordered hub proteins. The structure of native G-actin and inactivated actin were characterized both in aqueous solutions and in the presence of crowding agents (Dextran 70 and PEG 8000) modeling cellular milieu.