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Title: Hydrogen bonds are a primary driving force for de novo protein folding

Abstract

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 peptidemore » 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.« less

Authors:
 [1];  [2];  [1];  [3];  [3];  [2]; ORCiD logo [2];  [4];  [5]; ORCiD logo [1]; ORCiD logo [1];  [4];  [6];  [1]
  1. National Jewish Health, Denver, CO (United States); Univ. of Colorado, Aurora, CO (United States)
  2. National Jewish Health, Denver, CO (United States)
  3. Univ. of Missouri, Columbia, MO (United States)
  4. Univ. of Colorado, Aurora, CO (United States)
  5. Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States)
  6. Peking Union Medical College, Beijing (People's Republic of China)
Publication Date:
Research Org.:
Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States)
Sponsoring Org.:
USDOE Office of Science (SC)
OSTI Identifier:
1409879
Alternate Identifier(s):
OSTI ID: 1420134
Grant/Contract Number:  
AC02-05CH11231; AC03-76SF00098
Resource Type:
Journal Article: Published Article
Journal Name:
Acta Crystallographica. Section D. Structural Biology
Additional Journal Information:
Journal Volume: 73; Journal Issue: 12; Journal ID: ISSN 2059-7983
Publisher:
IUCr
Country of Publication:
United States
Language:
English
Subject:
59 BASIC BIOLOGICAL SCIENCES; hydrogen bonds; cis/trans-proline; protein folding

Citation Formats

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, and Zhang, Gongyi. Hydrogen bonds are a primary driving force for de novo protein folding. United States: N. p., 2017. Web. doi:10.1107/S2059798317015303.
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. United States. doi:10.1107/S2059798317015303.
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, and Zhang, Gongyi. Fri . "Hydrogen bonds are a primary driving force for de novo protein folding". United States. doi:10.1107/S2059798317015303.
@article{osti_1409879,
title = {Hydrogen bonds are a primary driving force for de novo protein folding},
author = {Lee, Schuyler and Wang, Chao and Liu, Haolin and Xiong, Jian and Jiji, Renee and Hong, Xia and Yan, Xiaoxue and Chen, Zhangguo and Hammel, Michal and Wang, Yang and Dai, Shaodong and Wang, Jing and Jiang, Chengyu and Zhang, Gongyi},
abstractNote = {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.},
doi = {10.1107/S2059798317015303},
journal = {Acta Crystallographica. Section D. Structural Biology},
number = 12,
volume = 73,
place = {United States},
year = {Fri Nov 10 00:00:00 EST 2017},
month = {Fri Nov 10 00:00:00 EST 2017}
}

Journal Article:
Free Publicly Available Full Text
Publisher's Version of Record at 10.1107/S2059798317015303

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Cited by: 1 work
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