期刊名称：Proceedings of the National Academy of Sciences
印刷版ISSN：0027-8424
电子版ISSN：1091-6490
出版年度：1999
卷号：96
期号：19
页码：10699-10704
DOI：10.1073/pnas.96.19.10699
语种：English
出版社：The National Academy of Sciences of the United States of America
摘要：We have investigated the folding behavior of dimeric and covalently crosslinked versions of the 33-residue -helical GCN4-p1 coiled coil derived from the leucine zipper region of the transcriptional activator GCN4. The effects of multisite substitutions indicate that folding occurs along multiple routes with nucleation sites located throughout the protein. The similarity in activation energies of the different routes together with an analysis of intrinsic helical propensities indicate that minimal helix is present before a productive collision of the two chains. However, approximately one-third to one-half of the total helical structure is formed in the postcollision transition state ensemble. For the crosslinked, monomeric version, folding occurs along a single robust pathway. Here, the region nearest the crosslink, with the least helical propensity, is structured in the transition state whereas the region farthest from the tether, with the most propensity, is completely unstructured. Hence, the existence of transition state heterogeneity and the selection of folding routes critically depend on chain topology.
