The major transition state in folding need not involve the immobilization of side chains

AUTOR(ES)

Staniforth, Rosemary A.

FONTE

The National Academy of Sciences

RESUMO

During protein folding in which few, if any, definable kinetic intermediates are observable, the nature of the transition state is central to understanding the course of the reaction. Current experimental data does not distinguish the relative contributions of side chain immobilization and dehydration phenomena to the major rate-limiting transition state whereas this distinction is central to theoretical models that attempt to simulate the behavior of proteins during folding. Renaturation of the small proteinase inhibitor cystatin under oxidizing versus reducing conditions is the first experimental case in which these processes can be studied independently. Using this example, we show that sidechain immobilization occurs downstream of the major folding transition state. A consequence of this is the existence of states with disordered side chains, which are distinct from kinetic protein folding intermediates and which lie within the folded state free energy well.

Documentos Relacionados

• The pKa of His-24 in the folding transition state of apomyoglobin
• Molecular dynamics simulations of protein folding from the transition state
• Single-molecule transition-state analysis of RNA folding
• Long-range order in the src SH3 folding transition state
• Differences in the folding transition state of ubiquitin indicated by φ and ψ analyses