Open AccessA protein folding pathway with multiple folding intermediates at atomic resolution
Author(s) -
Hanqiao Feng,
Zheng Zhou,
Yawen Bai
Publication year - 2005
Publication title -
proceedings of the national academy of sciences of the united states of america
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.011
H-Index - 771
eISSN - 1091-6490
pISSN - 0027-8424
DOI - 10.1073/pnas.0501372102
Subject(s) - protein folding , folding (dsp implementation) , phi value analysis , crystallography , helix (gastropod) , helix bundle , chemistry , protein structure , lattice protein , contact order , native state , topology (electrical circuits) , biology , biochemistry , ecology , snail , electrical engineering , engineering , mathematics , combinatorics
Using native-state hydrogen-exchange-directed protein engineering and multidimensional NMR, we determined the high-resolution structure (rms deviation, 1.1 angstroms) for an intermediate of the four-helix bundle protein: Rd-apocytochrome b562. The intermediate has the N-terminal helix and a part of the C-terminal helix unfolded. In earlier studies, we also solved the structures of two other folding intermediates for the same protein: one with the N-terminal helix alone unfolded and the other with a reorganized hydrophobic core. Together, these structures provide a description of a protein folding pathway with multiple intermediates at atomic resolution. The two general features for the intermediates are (i) native-like backbone topology and (ii) nonnative side-chain interactions. These results have implications for important issues in protein folding studies, including large-scale conformation search, -value analysis, and computer simulations.