Single versus parallel pathways of protein folding and fractional formation of structure in the transition state

TY - JOUR

T1 - Single versus parallel pathways of protein folding and fractional formation of structure in the transition state

AU - Fersht, Alan R.

AU - Itzhaki, Laura S.

AU - Elmasry, Nadia F.

AU - Matthews, Jacqueline M.

AU - Otzen, Daniel E.

PY - 1994/10/25

Y1 - 1994/10/25

N2 - Protein engineering and kinetic experiments indicate that some regions of proteins have partially formed structure in the transition state for protein folding. A crucial question is whether there is a genuine single transition state that has interactions that are weakened in those regions or there are parallel pathways involving many transition states, some with the interactions fully formed and others with the structural elements fully unfolded. We describe a kinetic test to distinguish between these possibilities. The kinetics rule out those mechanisms that involve a mixture of fully formed or fully unfolded structures for regions of the barley chymotrypsin inhibitor 2 and barnase, and so those regions are genuinely only partially folded in the transition state. The implications for modeling of protein folding pathways are discussed.

AB - Protein engineering and kinetic experiments indicate that some regions of proteins have partially formed structure in the transition state for protein folding. A crucial question is whether there is a genuine single transition state that has interactions that are weakened in those regions or there are parallel pathways involving many transition states, some with the interactions fully formed and others with the structural elements fully unfolded. We describe a kinetic test to distinguish between these possibilities. The kinetics rule out those mechanisms that involve a mixture of fully formed or fully unfolded structures for regions of the barley chymotrypsin inhibitor 2 and barnase, and so those regions are genuinely only partially folded in the transition state. The implications for modeling of protein folding pathways are discussed.

KW - barnase

KW - chymotrypsin inhibitor 2

KW - linear free-energy relationships

UR - http://www.scopus.com/inward/record.url?scp=0028037217&partnerID=8YFLogxK

U2 - 10.1073/pnas.91.22.10426

DO - 10.1073/pnas.91.22.10426

M3 - Journal article

C2 - 7937968

AN - SCOPUS:0028037217

SN - 0027-8424

VL - 91

SP - 10426

EP - 10429

JO - Proceedings of the National Academy of Sciences (PNAS)

JF - Proceedings of the National Academy of Sciences (PNAS)

IS - 22

ER -