B. Kundu et P. Guptasarma, Hydrophobic dye inhibits aggregation of molten carbonic anhydrase during thermal unfolding and refolding, PROTEINS, 37(3), 1999, pp. 321-324
Association-seeking surfaces on partially structured polypeptides can parti
cipate in interactions that are either intramolecular (folding related) or
intermolecular (aggregative). During heat shock, intermolecular association
s leading to aggregation are prevented through the binding of such surfaces
by chaperones of the Hsp20 family (with Hsp70 later effecting release and
refolding). Here we report that the hydrophobic dye, 8-anilino-1-naphthalen
esulfonate (ANS), mimics the function of the chaperones in its interactions
with molten carbonic anhydrase (CA),At 150-fold molar excess of dye over p
rotein, heat-induced aggregation of CA is almost completely inhibited by bi
nding of ANS to solvent-exposed clusters of nonpolar residues. After exposu
re of ANS-containing protein solutions to temperatures as high as 95 degree
s C, refolded CA can be recovered through cooling and dialysis, with no acc
ompanying aggregation. This apparent mimicking of chaperone activity by a s
mall dye opens up new approaches to understanding and manipulating protein
aggregation. Proteins 1999;37:321-324. (C) 1999 Wiley-Liss, Inc.