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The chaperonin cycle cannot substitute for prolyl isomerase activity, but GroEL alone promotes productive folding of a cyclophilin‐sensitive substrate to a cyclophilin‐resistant form
Author(s) -
von Ahsen Oliver,
Tropschug Maximilian,
Pfanner Nikolaus,
Rassow Joachim
Publication year - 1997
Publication title -
the embo journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.484
H-Index - 392
eISSN - 1460-2075
pISSN - 0261-4189
DOI - 10.1093/emboj/16.15.4568
Subject(s) - chaperonin , biology , peptidylprolyl isomerase , groel , prolyl isomerase , cyclophilin , cyclophilin a , protein folding , isomerase , folding (dsp implementation) , biochemistry , pin1 , biophysics , foldase , enzyme , microbiology and biotechnology , escherichia coli , gene , electrical engineering , engineering
The chaperonin GroEL and the peptidyl‐prolyl cis–trans isomerase cyclophilin are major representatives of two distinct cellular systems that help proteins to adopt their native three‐dimensional structure: molecular chaperones and folding catalysts. Little is known about whether and how these proteins cooperate in protein folding. In this study, we have examined the action of GroEL and cyclophilin on a substrate protein in two distinct prolyl isomerization states. Our results indicate that: (i) GroEL binds the same substrate in different prolyl isomerization states. (ii) GroEL–ES does not promote prolyl isomerizations, but even retards isomerizations. (iii) Cyclophilin cannot promote the correct isomerization of prolyl bonds of a GroEL‐bound substrate, but acts sequentially after release of the substrate from GroEL. (iv) A denatured substrate with all‐native prolyl bonds is delayed in folding by cyclophilin due to isomerization to non‐native prolyl bonds; a substrate that has proceeded in folding beyond a stage where it can be bound by GroEL is still sensitive to cyclophilin. (v) If a denatured cyclophilin‐sensitive substrate is first bound to GroEL, however, productive folding to a cyclophilin‐resistant form can be promoted, even without GroES. We conclude that GroEL and cyclophilin act sequentially and exert complementary functions in protein folding.