Mapping long-range contacts in a highly unfolded protein.
Insights into the earliest events in protein folding can be obtained by analysis of the conformational propensities of unfolded or partly folded states. The structure of the acid-unfolded state of apomyoglobin has been characterized using paramagnetic spin labeling and NMR. Nitroxide side-chains, introduced by coupling to mutant cysteine residues at positions 18, 77, and 133, were used as probes of chain compaction and long-range tertiary contacts. Significant interactions are observed within and between the N and C termini, while the central region of the polypeptide chain behaves as a random polymer. Even in this highly denatured form, the protein samples transient compact states in which there are native-like contacts between the N and C-terminal regions.
Lietzow
Michael A
MA
Department of Molecular Biology and Skaggs Institute for Chemical Biology, The Scripps Research Institute, La Jolla, CA 92037, USA.
Jamin
Marc
M
Dyson
H Jane
HJ
Wright
Peter E
PE
D001059:Apoproteins / Q000737:chemistry* / Q000235:genetics; D016296:Mutagenesis; D009211:Myoglobin / Q000737:chemistry* / Q000235:genetics; D017510:Protein Folding; D017434:Protein Structure, Tertiary; D013113:Spin Labels
D001059:Apoproteins; D009211:Myoglobin; D013113:Spin Labels; C010857:apomyoglobin