THE DIPYRIDYLS PARAQUAT AND DIQUAT ATTENUATE THE INTERACTION OF G-ACTIN WITH THYMOSIN-BETA(4)

beta-Thymosins sequester G-actin and preserve a pool of monomers of ac tin which constitute an important prerequisite for cellular function o f the microfilament system. To study the influence of paraquat binding to G-actin on the interaction of G-actin with thymosin beta(4) we det ermined the apparent dissociation constant of the G-actin-thymosin bet a(4) complex in the absence or presence of paraquat using an ultrafilt ration assay, Paraquat (1,1'-dimethyl-4,4'-dipyridylium dichloride) at tenuates this interaction in a concentration-and time-dependent manner . When exposed to 10 mM paraquat, the apparent dissociation constant i ncreased 10-85-fold within 15 min to 23 h, After incubation for 23 h e ven a paraquat concentration as low as 100 mu M increased the dissocia tion constant of the G-actin-thymosin beta(4) complex from 0.66 mu M t o 0.82 mu M (P < 0.05), Diquat (1,1'-ethylene-2,2'-dipyridylium dibrom ide) similarly weakens the interaction of G-actin and beta-thymosins, In none of the experiments was oxidation of the methionine residue or any other modification of thymosin beta(4) detected. Therefore we conc lude that the dipyridyls paraquat and diquat directly interact with G- actin and thereby impede the interaction between G-actin and thymosin beta(4). (C) 1998 Federation of European Biochemical Societies.