2003年4月
Testing the relationship between foldability and the early folding events of dihydrofolate reductase from Escherichia coli
JOURNAL OF MOLECULAR BIOLOGY
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- ,
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- 巻
- 328
- 号
- 1
- 開始ページ
- 273
- 終了ページ
- 288
- 記述言語
- 英語
- 掲載種別
- DOI
- 10.1016/S0022-2836(03)00212-2
- 出版者・発行元
- ACADEMIC PRESS LTD ELSEVIER SCIENCE LTD
A "folding element" is a contiguous peptide segment crucial for a protein to be foldable and is a new concept that could assist in our understanding of the protein-folding problem. It is known that the presence of the complete set of folding elements of dihydrofolate reductase (DHFR) from Escherichia coli is essential for the protein to be foldable. Since almost all of the amino acid residues known to be involved in the early folding events of DHFR are located within the folding elements, a close relationship between the folding elements and early folding events is hypothesized. In order to test this hypothesis, we have investigated whether or not the early folding events are preserved in circular permutants and topological mutants of DHFR, in which the order of the folding elements is changed but the complete set of folding elements is present. The stopped-flow circular dichroism (CD) measurements show that the CD spectra at the early stages of folding are similar among the mutants and the wild-type DHFR, indicating that the presence of the complete set of folding elements is sufficient to preserve the early folding events. We have further examined whether or not sequence perturbation on the folding elements by a single amino acid substitution affects the early folding events of DHFR. The results show that the amino acid substitutions inside of the folding elements can affect the burst-phase CD spectra, whereas the substitutions outside do not. Taken together, these results indicate that the above hypothesis is true, suggesting a close relationship between the foldability of a protein and the early folding events. We propose that the folding elements interact with each other and coalesce to form a productive intermediate(s) early in the folding, and these early folding events are important for a protein to be foldable. (C) 2003 Elsevier Science Ltd. All rights reserved.
- リンク情報
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- DOI
- https://doi.org/10.1016/S0022-2836(03)00212-2
- CiNii Articles
- http://ci.nii.ac.jp/naid/80015888560
- PubMed
- https://www.ncbi.nlm.nih.gov/pubmed/12684013
- Web of Science
- https://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=JSTA_CEL&SrcApp=J_Gate_JST&DestLinkType=FullRecord&KeyUT=WOS:000182277200021&DestApp=WOS_CPL
- ID情報
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- DOI : 10.1016/S0022-2836(03)00212-2
- ISSN : 0022-2836
- CiNii Articles ID : 80015888560
- PubMed ID : 12684013
- Web of Science ID : WOS:000182277200021