ArticleProceedings of the National Academy of Sciences of the United States of America2012
Separating the effects of internal friction and transition state energy to explain the slow, frustrated folding of spectrin domains.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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Who cites it
19 citing papers in PubMed.
- Cotranslational folding cooperativity of contiguous domains of α-spectrin.Proceedings of the National Academy of Sciences of the United States of America · 2020Article
- Friction-Limited Folding of Disulfide-Reduced Monomeric SOD1.Biophysical journal · 2020Article
- Size and topology modulate the effects of frustration in protein folding.Proceedings of the National Academy of Sciences of the United States of America · 2018Article
- Transition Path Times Measured by Single-Molecule Spectroscopy.Journal of molecular biology · 2018Review
- Kinetic and thermodynamic studies reveal chemokine homologues CC11 and CC24 with an almost identical tertiary structure have different folding pathways.BMC biophysics · 2017Article
- Modulation of Folding Internal Friction by Local and Global Barrier Heights.The journal of physical chemistry letters · 2016Article
- Article
- Structural origin of slow diffusion in protein folding.Science (New York, N.Y.) · 2015Article
- Mechanistic studies of the biogenesis and folding of outer membrane proteins in vitro and in vivo: what have we learned to date?Archives of biochemistry and biophysics · 2014Review
- Folding pathway of a multidomain protein depends on its topology of domain connectivity.Proceedings of the National Academy of Sciences of the United States of America · 2014Article
- Frustration in biomolecules.Quarterly reviews of biophysics · 2014Review
- The folding of a family of three-helix bundle proteins: spectrin R15 has a robust folding nucleus, unlike its homologous neighbours.Journal of molecular biology · 2014Article
- Assessment of local friction in protein folding dynamics using a helix cross-linker.The journal of physical chemistry. B · 2013Article
- How well does a funneled energy landscape capture the folding mechanism of spectrin domains?The journal of physical chemistry. B · 2013Article
- Membrane proteins can have high kinetic stability.Journal of the American Chemical Society · 2013Article
- Take home lessons from studies of related proteins.Current opinion in structural biology · 2013Review
- Chemical physics of protein folding.Proceedings of the National Academy of Sciences of the United States of America · 2012Article
- Protein folding: adding a nucleus to guide helix docking reduces landscape roughness.Journal of molecular biology · 2012Article
- Localizing internal friction along the reaction coordinate of protein folding by combining ensemble and single-molecule fluorescence spectroscopy.Nature communications · 2012Article
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7 authors.
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Abstract
The elongated three-helix bundle domains spectrin R16 and R17 fold some two to three orders of magnitude more slowly than their homologue R15. We have shown that this slow folding is due, at least in part, to roughness in the free-energy landscape of R16 and R17. We have proposed that this roughness is due to a frustrated search for the correct docking of partly preformed helices. However, this accounts for only a small part of the slowing of folding and unfolding. Five residues on the A helix of R15, when inserted together into R16 or R17, increase the folding rate constants, reduce landscape roughness, and alter the folding mechanism to one resembling R15. The effect of each of these mutations individually is investigated here. No one mutation causes the behavior seen for the five in combination. However, two mutations, E18F and K25V, significantly increase the folding and unfolding rates of both R16 and R17 but without a concomitant loss in landscape roughness. E18F has the greatest effect on the kinetics, and a Φ-value analysis of the C helix reveals that the folding mechanism is unchanged. For both E18F and K25V the removal of the charge and resultant transition state stabilization is the main origin of the faster folding. Consequently, the major cause of the unusually slow folding of R16 and R17 is the non-native burial of the two charged residues in the transition state. The slowing due to landscape roughness is only about fivefold.
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