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Letter from Chen-Lu Tsou to Joshua Lederberg

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  • Biology
  • Chemistry
  • Medicine
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THE ROCKEFELLER UNIVERSITY 1230YORK AVENUE NEW YORK, NY 10021 May.6, 1988 IOSHUA LEDERBERG PRESIDENT Professor Chen-Lu Tsou Laboratory of Molecular Enzymology Institute of Biophysics Academia Sinica Beijing 100080 China Dear Professor Tsou: I read with great interest your paper on protein folding that appeared in Biochemistry, March 22, 1988. Although I do not actively'conduct this' field',your letter raises issues that have been of very great interest to me for the past 30 years. If folding is concurrent with translation I would expect that, as yousay, post-translational adjustments would ensue to bring the completed chain into its final, lowest energy state. I am going to raise a slightly different argument, how- ever, about whether this final lowest energy state is the bioloaicallv active state. As you point out the approach to equilibrium from the renatured state may be a lengthy process and in principle there may be kinetic constraints that will require many hours or perhaps even virtually infinite time. The plausible possibility that I then pose to you is that many proteins will be in their biologically active (and evo- lutionary selected)conformation. for a period of seconds to minutes,anslation is completed,but that they can then undergo further transitions to the thermodynamic limit, which is not necessarily-biologically active. In that case there will have been many frustrations to protein chemists seeking to isolate proteins that retain their biologically active ccqfn.qation, when the equilibrium conformer, stab12 after isolation and over long periods of storage,may well be bio- logically inactive. 'Certainly it is no part of the evolu- tionary process that protein.products?etain their most active conformation to suit the convenience of biochemists. Professor Chen-Lu Tsou May 10, 1988 -2- What I don't know is whether there is tangible experimen- tal evidence to support this conjecture

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