Research Topic

Biophysics of Co-Translational Protein Folding

About this Research Topic

Protein folding is typically viewed from the ground truth of Anfinsen’s thermodynamic hypothesis, which states that native states are thermodynamic minima; this implies that proteins should be able to reliably navigate to their native forms irrespective of their history. In the cell, however, proteins fold whilst they are being synthesized on the ribosome. It has long been appreciated that this feature is significant for membrane targeting and other cellular processes, but recent research suggests that co-translational folding can be critical for: (i) avoiding kinetically-trapped misfolded states; (ii) mediating multi-domain folding; (iii) assembling multi subunit complexes; or (iv) utilizing certain chaperones appropriately. Hence the biophysical relevance of translation for folding more complex ‘non-model’ proteins is coming into view.

Our understanding of protein folding, misfolding, and aggregation is changing. Protein folding, long interpreted through the lens of biophysical refolding experiments on small proteins and typically conforming to two-state models, may be a poor model for folding in vivo, which occurs co-translationally. The importance of co-translational folding has recently become more widely appreciated, and several methods (both experimental and computational) have been developed that now make this complicated phenomenon easier to interrogate. The three goals of this research topic are: (i) to celebrate new and emerging approaches to investigate co-translational protein folding; (ii) to showcase results that emphasize the importance of translation in folding particular (types of) proteins; (iii) to emphasize the kinetic aspects of protein folding, and (iv) to critically elucidate differences between protein folding in vivo compared to traditional in vitro refolding assays so as to shed light as to where our ‘received truths’ about protein folding might need to be reconsidered.

This Research Topic welcomes Mini Reviews, Original Research, and Perspective articles investigating the biophysics of co-translation protein folding. Themes of interest could include, but are not limited to;

• New experimental techniques to interrogate co-translational protein folding (e.g., force profile analysis, single-molecule studies)
• New computational approaches to interrogate co-translational folding (e.g., course-grained models, Markov chain models)
• New findings reporting on translation mediating aspects of ‘higher-level’ protein assembly and organization
• Pieces that characterize differences between co-translational folding and in vitro refolding
• Discussions of irreversible or energy-dissipating processes during protein folding


Keywords: Protein Folding, Biophysics, Co-Translational, Experiments, Computational, Assembly


Important Note: All contributions to this Research Topic must be within the scope of the section and journal to which they are submitted, as defined in their mission statements. Frontiers reserves the right to guide an out-of-scope manuscript to a more suitable section or journal at any stage of peer review.

Protein folding is typically viewed from the ground truth of Anfinsen’s thermodynamic hypothesis, which states that native states are thermodynamic minima; this implies that proteins should be able to reliably navigate to their native forms irrespective of their history. In the cell, however, proteins fold whilst they are being synthesized on the ribosome. It has long been appreciated that this feature is significant for membrane targeting and other cellular processes, but recent research suggests that co-translational folding can be critical for: (i) avoiding kinetically-trapped misfolded states; (ii) mediating multi-domain folding; (iii) assembling multi subunit complexes; or (iv) utilizing certain chaperones appropriately. Hence the biophysical relevance of translation for folding more complex ‘non-model’ proteins is coming into view.

Our understanding of protein folding, misfolding, and aggregation is changing. Protein folding, long interpreted through the lens of biophysical refolding experiments on small proteins and typically conforming to two-state models, may be a poor model for folding in vivo, which occurs co-translationally. The importance of co-translational folding has recently become more widely appreciated, and several methods (both experimental and computational) have been developed that now make this complicated phenomenon easier to interrogate. The three goals of this research topic are: (i) to celebrate new and emerging approaches to investigate co-translational protein folding; (ii) to showcase results that emphasize the importance of translation in folding particular (types of) proteins; (iii) to emphasize the kinetic aspects of protein folding, and (iv) to critically elucidate differences between protein folding in vivo compared to traditional in vitro refolding assays so as to shed light as to where our ‘received truths’ about protein folding might need to be reconsidered.

This Research Topic welcomes Mini Reviews, Original Research, and Perspective articles investigating the biophysics of co-translation protein folding. Themes of interest could include, but are not limited to;

• New experimental techniques to interrogate co-translational protein folding (e.g., force profile analysis, single-molecule studies)
• New computational approaches to interrogate co-translational folding (e.g., course-grained models, Markov chain models)
• New findings reporting on translation mediating aspects of ‘higher-level’ protein assembly and organization
• Pieces that characterize differences between co-translational folding and in vitro refolding
• Discussions of irreversible or energy-dissipating processes during protein folding


Keywords: Protein Folding, Biophysics, Co-Translational, Experiments, Computational, Assembly


Important Note: All contributions to this Research Topic must be within the scope of the section and journal to which they are submitted, as defined in their mission statements. Frontiers reserves the right to guide an out-of-scope manuscript to a more suitable section or journal at any stage of peer review.

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Submission Deadlines

10 January 2022 Manuscript

Participating Journals

Manuscripts can be submitted to this Research Topic via the following journals:

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Topic Editors

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Submission Deadlines

10 January 2022 Manuscript

Participating Journals

Manuscripts can be submitted to this Research Topic via the following journals:

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