ArticleProceedings of the National Academy of Sciences of the United States of America2013
Exploring the nature of the translocon-assisted protein insertion.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2013. 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.
- The Molecular Biodiversity of Protein Targeting and Protein Transport Related to the Endoplasmic Reticulum.International journal of molecular sciences · 2021Review
- Molecular Modeling of Signal Peptide Recognition by Eukaryotic Sec Complexes.International journal of molecular sciences · 2021Review
- How does Sec63 affect the conformation of Sec61 in yeast?PLoS computational biology · 2021Article
- Dynamics of Co-translational Membrane Protein Integration and Translocation via the Sec Translocon.Journal of the American Chemical Society · 2020Review
- Multiscale Simulations of Biological Membranes: The Challenge To Understand Biological Phenomena in a Living Substance.Chemical reviews · 2019Article
- Identification of Putative Substrates of SEC2, a Chloroplast Inner Envelope Translocase.Plant physiology · 2017Article
- Structurally detailed coarse-grained model for Sec-facilitated co-translational protein translocation and membrane integration.PLoS computational biology · 2017Article
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- Recent advances in QM/MM free energy calculations using reference potentials.Biochimica et biophysica acta · 2015Review
- Lateral opening of the bacterial translocon on ribosome binding and signal peptide insertion.Nature communications · 2014Article
- Multiscale modeling of biological functions: from enzymes to molecular machines (Nobel Lecture).Angewandte Chemie (International ed. in English) · 2014Article
- Implicit membrane treatment of buried charged groups: application to peptide translocation across lipid bilayers.Biochimica et biophysica acta · 2014Article
- An effective coarse-grained model for biological simulations: recent refinements and validations.Proteins · 2014Article
- Coarse-grained simulations of the gating current in the voltage-activated Kv1.2 channel.Proceedings of the National Academy of Sciences of the United States of America · 2014Article
- Functional asymmetry within the Sec61p translocon.Proceedings of the National Academy of Sciences of the United States of America · 2013Article
- On the nature of the apparent free energy of inserting amino acids into membrane through the translocon.The journal of physical chemistry. B · 2013Article
- Simulating the pulling of stalled elongated peptide from the ribosome by the translocon.Proceedings of the National Academy of Sciences of the United States of America · 2013Article
- In vitro reconstitution of lipid-dependent dual topology and postassembly topological switching of a membrane protein.Proceedings of the National Academy of Sciences of the United States of America · 2013Article
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2 authors.
Funding
Abstract
The elucidation of the molecular nature of the translocon-assisted protein insertion is a challenging problem due to the complexity of this process. Furthermore, the limited availability of crucial structural information makes it hard to interpret the hints about the insertion mechanism provided by biochemical studies. At present, it is not practical to explore the insertion process by brute force simulation approaches due to the extremely lengthy process and very complex landscape. Thus, this work uses our previously developed coarse-grained model and explores the energetics of the membrane insertion and translocation paths. The trend in the calculated free-energy profiles is verified by evaluating the correlation between the calculated and observed effect of mutations as well as the effect of inverting the signal peptide that reflects the "positive-inside" rule. Furthermore, the effect of the tentative opening induced by the ribosome is found to reduce the kinetic barrier. Significantly, the trend of the forward and backward energy barriers provides a powerful way to analyze key energetics information. Thus, it is concluded that the insertion process is most likely a nonequilibrium process. Moreover, we provided a general formulation for the analysis of the elusive apparent membrane insertion energy, ΔG(app), and conclude that this important parameter is unlikely to correspond to the free-energy difference between the translocon and membrane. Our formulation seems to resolve the controversy about ΔG(app) for Arg.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.