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Hydrogen bonds are a primary driving force for de novo protein folding
The protein-folding mechanism remains a major puzzle in life science. Purified soluble activation-induced cytidine deaminase (AID) is one of the most difficult proteins to obtain. Starting from inclusion bodies containing a C-terminally truncated version of AID (residues 1–153; AID(153)), an optimiz...
Autores principales: | , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
International Union of Crystallography
2017
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5713874/ https://www.ncbi.nlm.nih.gov/pubmed/29199976 http://dx.doi.org/10.1107/S2059798317015303 |
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author | Lee, Schuyler Wang, Chao Liu, Haolin Xiong, Jian Jiji, Renee Hong, Xia Yan, Xiaoxue Chen, Zhangguo Hammel, Michal Wang, Yang Dai, Shaodong Wang, Jing Jiang, Chengyu Zhang, Gongyi |
author_facet | Lee, Schuyler Wang, Chao Liu, Haolin Xiong, Jian Jiji, Renee Hong, Xia Yan, Xiaoxue Chen, Zhangguo Hammel, Michal Wang, Yang Dai, Shaodong Wang, Jing Jiang, Chengyu Zhang, Gongyi |
author_sort | Lee, Schuyler |
collection | PubMed |
description | The protein-folding mechanism remains a major puzzle in life science. Purified soluble activation-induced cytidine deaminase (AID) is one of the most difficult proteins to obtain. Starting from inclusion bodies containing a C-terminally truncated version of AID (residues 1–153; AID(153)), an optimized in vitro folding procedure was derived to obtain large amounts of AID(153), which led to crystals with good quality and to final structural determination. Interestingly, it was found that the final refolding yield of the protein is proline residue-dependent. The difference in the distribution of cis and trans configurations of proline residues in the protein after complete denaturation is a major determining factor of the final yield. A point mutation of one of four proline residues to an asparagine led to a near-doubling of the yield of refolded protein after complete denaturation. It was concluded that the driving force behind protein folding could not overcome the cis-to-trans proline isomerization, or vice versa, during the protein-folding process. Furthermore, it was found that successful refolding of proteins optimally occurs at high pH values, which may mimic protein folding in vivo. It was found that high pH values could induce the polarization of peptide bonds, which may trigger the formation of protein secondary structures through hydrogen bonds. It is proposed that a hydrophobic environment coupled with negative charges is essential for protein folding. Combined with our earlier discoveries on protein-unfolding mechanisms, it is proposed that hydrogen bonds are a primary driving force for de novo protein folding. |
format | Online Article Text |
id | pubmed-5713874 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2017 |
publisher | International Union of Crystallography |
record_format | MEDLINE/PubMed |
spelling | pubmed-57138742017-12-13 Hydrogen bonds are a primary driving force for de novo protein folding Lee, Schuyler Wang, Chao Liu, Haolin Xiong, Jian Jiji, Renee Hong, Xia Yan, Xiaoxue Chen, Zhangguo Hammel, Michal Wang, Yang Dai, Shaodong Wang, Jing Jiang, Chengyu Zhang, Gongyi Acta Crystallogr D Struct Biol Research Papers The protein-folding mechanism remains a major puzzle in life science. Purified soluble activation-induced cytidine deaminase (AID) is one of the most difficult proteins to obtain. Starting from inclusion bodies containing a C-terminally truncated version of AID (residues 1–153; AID(153)), an optimized in vitro folding procedure was derived to obtain large amounts of AID(153), which led to crystals with good quality and to final structural determination. Interestingly, it was found that the final refolding yield of the protein is proline residue-dependent. The difference in the distribution of cis and trans configurations of proline residues in the protein after complete denaturation is a major determining factor of the final yield. A point mutation of one of four proline residues to an asparagine led to a near-doubling of the yield of refolded protein after complete denaturation. It was concluded that the driving force behind protein folding could not overcome the cis-to-trans proline isomerization, or vice versa, during the protein-folding process. Furthermore, it was found that successful refolding of proteins optimally occurs at high pH values, which may mimic protein folding in vivo. It was found that high pH values could induce the polarization of peptide bonds, which may trigger the formation of protein secondary structures through hydrogen bonds. It is proposed that a hydrophobic environment coupled with negative charges is essential for protein folding. Combined with our earlier discoveries on protein-unfolding mechanisms, it is proposed that hydrogen bonds are a primary driving force for de novo protein folding. International Union of Crystallography 2017-11-10 /pmc/articles/PMC5713874/ /pubmed/29199976 http://dx.doi.org/10.1107/S2059798317015303 Text en © Lee et al. 2017 http://creativecommons.org/licenses/by/2.0/uk/ This is an open-access article distributed under the terms of the Creative Commons Attribution (CC-BY) Licence, which permits unrestricted use, distribution, and reproduction in any medium, provided the original authors and source are cited.http://creativecommons.org/licenses/by/2.0/uk/ |
spellingShingle | Research Papers Lee, Schuyler Wang, Chao Liu, Haolin Xiong, Jian Jiji, Renee Hong, Xia Yan, Xiaoxue Chen, Zhangguo Hammel, Michal Wang, Yang Dai, Shaodong Wang, Jing Jiang, Chengyu Zhang, Gongyi Hydrogen bonds are a primary driving force for de novo protein folding |
title | Hydrogen bonds are a primary driving force for de novo protein folding |
title_full | Hydrogen bonds are a primary driving force for de novo protein folding |
title_fullStr | Hydrogen bonds are a primary driving force for de novo protein folding |
title_full_unstemmed | Hydrogen bonds are a primary driving force for de novo protein folding |
title_short | Hydrogen bonds are a primary driving force for de novo protein folding |
title_sort | hydrogen bonds are a primary driving force for de novo protein folding |
topic | Research Papers |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5713874/ https://www.ncbi.nlm.nih.gov/pubmed/29199976 http://dx.doi.org/10.1107/S2059798317015303 |
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