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- Title
Knot formation in newly translated proteins is spontaneous and accelerated by chaperonins.
- Authors
Mallam, Anna L; Jackson, Sophie E
- Abstract
Topological knots are found in a considerable number of protein structures, but it is not clear how they knot and fold within the cellular environment. We investigated the behavior of knotted protein molecules as they are first synthesized by the ribosome using a cell-free translation system. We found that newly translated knotted proteins can spontaneously self-tie and do not require the assistance of molecular chaperones to fold correctly to their trefoil-knotted structures. This process is slow but efficient, and we found no evidence of misfolded species. A kinetic analysis indicates that the knotting process is rate limiting, occurs post-translationally, and is specifically and significantly (P < 0.001) accelerated by the GroEL-GroES chaperonin complex. This demonstrates a new active mechanism for this molecular chaperone and suggests that chaperonin-catalyzed knotting probably dominates in vivo. These results explain how knotted protein structures have withstood evolutionary pressures despite their topological complexity.
- Subjects
AMINO acid sequence; NATURAL selection; ADENOSYLMETHIONINE; MOLECULAR chaperones; LINEAR free energy relationship; RIBOSOMES
- Publication
Nature Chemical Biology, 2012, Vol 8, Issue 2, p147
- ISSN
1552-4450
- Publication type
Article
- DOI
10.1038/nchembio.742