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Hydrogen bonds are a primary driving force for de novo protein folding
Author(s) -
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
Publication year - 2017
Publication title -
acta crystallographica section d
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.374
H-Index - 138
ISSN - 2059-7983
DOI - 10.1107/s2059798317015303
Subject(s) - protein folding , chemistry , lattice protein , hydrogen bond , denaturation (fissile materials) , phi value analysis , asparagine , protein secondary structure , barnase , crystallography , protein structure , peptide bond , biophysics , protein engineering , peptide , biochemistry , ribonuclease , molecule , enzyme , organic chemistry , biology , rna , gene , nuclear chemistry
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.