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Threading a peptide through a peptide: Protein loops, rotaxanes, and knots
Author(s) -
Blankenship John W.,
Dawson Philip E.
Publication year - 2007
Publication title -
protein science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.353
H-Index - 175
eISSN - 1469-896X
pISSN - 0961-8368
DOI - 10.1110/ps.062673207
Subject(s) - threading (protein sequence) , rotaxane , peptide , folding (dsp implementation) , protein folding , crystallography , chemistry , supramolecular chemistry , kinetics , native chemical ligation , biophysics , protein structure , biology , biochemistry , physics , chemical synthesis , crystal structure , quantum mechanics , electrical engineering , engineering , in vitro
Proteins adopt complex folds in nature that typically avoid conformations that are knotted or “threaded” through closed loops. Is this the result of fundamental barriers to folding, or have proteins simply evolved to avoid threaded conformations? Organic synthesis has been used in supramolecular chemistry to install topological links in small molecules. By following these principles, we now show that it is possible to assemble a topologically linked protein complex by threading a linear protein through a cyclic protein to form a [2]pseudo‐rotaxane. Subsequent ring closure using native chemical ligation cyclizes the linear protein, forming a [2]heterocatenane. Although the kinetics of protein threading are slower than the folding kinetics of the native protein, threading appears to be a highly efficient process.