Folding and Assembly of Short α, β, γ-Hybrid Peptides: Minor Variations in Sequence and Drastic Differences in Higher-Level Structures

Zhang, Yukun; Zhong, Yulong; Connor, Alan L.; Miller, Daniel P.; Cao, Ruikai; Shen, Jie; Song, Bo; Baker, Erin S.; Tang, Quan; Pulavarti, Surya V. S. R. K.; Liu, Rui; Wang, Qiwei; Lu, Zhong-lin; Szyperski, Thomas; Zeng, Huaqiang; Li, Xiaopeng; Smith, Richard D.; Zurek, Eva; Zhu, Jin; Gong, Bing

doi:10.1021/jacs.9b06094

Title: Folding and Assembly of Short α, β, γ-Hybrid Peptides: Minor Variations in Sequence and Drastic Differences in Higher-Level Structures

Abstract

Multilevel protein structures typically involve polypeptides of sufficient lengths. Here we report the folding and assembly of seven short tetrapeptides sharing the same types of a-, ß-, and aromatic ?-amino acid residues. These are two sets of hybrid peptides, with three members in one set and four in the other, having complementary hydrogen-bonding sequences that were hypothesized to pair into linear H-bonded duplexes. However, instead of undergoing the anticipated pairing, the initially examined three oligomers, 1 and 2a or 2b, differing only in their central aß hybrid dipeptide sequence, do not associate with each other and exhibit distinctly different folding behavior. Experiments based on NMR and mass spectrometry, along with computational studies and systematic inference, reveal that oligomer 1 folds into an expanded ß-turn containing an unusual hybrid a/ß-amino acid sequence composed of glycine and ß-alanine, two a- and ß-amino acid residues that are conformationally most flexible, and peptides 2a and 2b adopt a noncanonical, extended helical conformation and dimerize into double helices undergoing rapid conformational exchange or helix inversion. The different central dipeptide sequences, aß vs ßa, result in drastically different intramolecular H-bonding patterns that are responsible for the observed folding behavior of 1 and 2. The revealed turnmore »« less

Authors:

Zhang, Yukun ^[1]; Zhong, Yulong ^[2]; Connor, Alan L. ^[2];

^[2]; Cao, Ruikai ^[2]; Shen, Jie ^[3];

^[4];

^[5]; Tang, Quan ^[6]; Pulavarti, Surya V. S. R. K. ^[2]; Liu, Rui ^[6]; Wang, Qiwei ^[7]; Lu, Zhong-lin ^[6]; Szyperski, Thomas ^[2];

^[3];

^[4]; Smith, Richard D. ^[5];

^[2]; Zhu, Jin ^[7];

^[2]

Chinese Academy of Sciences, Chengdu (China); Univ. of Chinese Academy of Sciences, Beijing (China)
Univ. at Buffalo, The State Univ. of New York, Buffalo, NY (United States)
The NanoBio Lab, The Nanos (Singapore)
Univ. of South Florida, Tampa, FL (United States)
Pacific Northwest National Lab. (PNNL), Richland, WA (United States)
Beijing Normal Univ., Beijing (China)
Chinese Academy of Sciences, Chengdu (China)

Publication Date:: Mon Aug 05 00:00:00 EDT 2019

Research Org.:: Pacific Northwest National Lab. (PNNL), Richland, WA (United States)

Sponsoring Org.:: USDOE

OSTI Identifier:: 1572955

Alternate Identifier(s):: OSTI ID: 1729882

Report Number(s):: PNNL-SA-146170; PNNL-SA-140660
Journal ID: ISSN 0002-7863

Grant/Contract Number:: AC05-76RL01830

Resource Type:: Accepted Manuscript

Journal Name:: Journal of the American Chemical Society

Additional Journal Information:: Journal Volume: 141; Journal Issue: 36; Journal ID: ISSN 0002-7863

Publisher:: American Chemical Society (ACS)

Country of Publication:: United States

Language:: English

Subject:: 37 INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CHEMISTRY

Citation Formats


                    Zhang, Yukun, Zhong, Yulong, Connor, Alan L., Miller, Daniel P., Cao, Ruikai, Shen, Jie, Song, Bo, Baker, Erin S., Tang, Quan, Pulavarti, Surya V. S. R. K., Liu, Rui, Wang, Qiwei, Lu, Zhong-lin, Szyperski, Thomas, Zeng, Huaqiang, Li, Xiaopeng, Smith, Richard D., Zurek, Eva, Zhu, Jin, and Gong, Bing. Folding and Assembly of Short α, β, γ-Hybrid Peptides: Minor Variations in Sequence and Drastic Differences in Higher-Level Structures.  United States: N. p., 2019. 
Web.  doi:10.1021/jacs.9b06094.

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                    Zhang, Yukun, Zhong, Yulong, Connor, Alan L., Miller, Daniel P., Cao, Ruikai, Shen, Jie, Song, Bo, Baker, Erin S., Tang, Quan, Pulavarti, Surya V. S. R. K., Liu, Rui, Wang, Qiwei, Lu, Zhong-lin, Szyperski, Thomas, Zeng, Huaqiang, Li, Xiaopeng, Smith, Richard D., Zurek, Eva, Zhu, Jin, & Gong, Bing. Folding and Assembly of Short α, β, γ-Hybrid Peptides: Minor Variations in Sequence and Drastic Differences in Higher-Level Structures.  United States.  https://doi.org/10.1021/jacs.9b06094

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                    Zhang, Yukun, Zhong, Yulong, Connor, Alan L., Miller, Daniel P., Cao, Ruikai, Shen, Jie, Song, Bo, Baker, Erin S., Tang, Quan, Pulavarti, Surya V. S. R. K., Liu, Rui, Wang, Qiwei, Lu, Zhong-lin, Szyperski, Thomas, Zeng, Huaqiang, Li, Xiaopeng, Smith, Richard D., Zurek, Eva, Zhu, Jin, and Gong, Bing. Mon .  
"Folding and Assembly of Short α, β, γ-Hybrid Peptides: Minor Variations in Sequence and Drastic Differences in Higher-Level Structures".  United States.  https://doi.org/10.1021/jacs.9b06094.  https://www.osti.gov/servlets/purl/1572955.

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@article{osti_1572955,

  title        = {Folding and Assembly of Short α, β, γ-Hybrid Peptides: Minor Variations in Sequence and Drastic Differences in Higher-Level Structures},

  author       = {Zhang, Yukun and Zhong, Yulong and Connor, Alan L. and Miller, Daniel P. and Cao, Ruikai and Shen, Jie and Song, Bo and Baker, Erin S. and Tang, Quan and Pulavarti, Surya V. S. R. K. and Liu, Rui and Wang, Qiwei and Lu, Zhong-lin and Szyperski, Thomas and Zeng, Huaqiang and Li, Xiaopeng and Smith, Richard D. and Zurek, Eva and Zhu, Jin and Gong, Bing},

  abstractNote = {Multilevel protein structures typically involve polypeptides of sufficient lengths. Here we report the folding and assembly of seven short tetrapeptides sharing the same types of a-, ß-, and aromatic ?-amino acid residues. These are two sets of hybrid peptides, with three members in one set and four in the other, having complementary hydrogen-bonding sequences that were hypothesized to pair into linear H-bonded duplexes. However, instead of undergoing the anticipated pairing, the initially examined three oligomers, 1 and 2a or 2b, differing only in their central aß hybrid dipeptide sequence, do not associate with each other and exhibit distinctly different folding behavior. Experiments based on NMR and mass spectrometry, along with computational studies and systematic inference, reveal that oligomer 1 folds into an expanded ß-turn containing an unusual hybrid a/ß-amino acid sequence composed of glycine and ß-alanine, two a- and ß-amino acid residues that are conformationally most flexible, and peptides 2a and 2b adopt a noncanonical, extended helical conformation and dimerize into double helices undergoing rapid conformational exchange or helix inversion. The different central dipeptide sequences, aß vs ßa, result in drastically different intramolecular H-bonding patterns that are responsible for the observed folding behavior of 1 and 2. The revealed turn and double helix have few natural or synthetic counterparts, and provide novel and unique folding prototypes based on which chiral a- and ß-amino acids are incorporated. The resultant derivatives 1a, 1b, 2c, and 2d follow the same folding and assembling behavior and demonstrate the generality of this system with the formation of expanded ß-turns and double helices with enhanced folding stabilities, hampered helix inversion, as well as defined and dominant helical sense. This work has demonstrated the unique capability of synthetic foldamers in generating structures with fascinating folding and assembling behavior. The revealed systems offer ample opportunity for further structural optimization and applications.},

  doi          = {10.1021/jacs.9b06094},

  journal      = {Journal of the American Chemical Society},

  number       = 36,

  volume       = 141,

  place        = {United States},

  year         = {Mon Aug 05 00:00:00 EDT 2019},

  month        = {Mon Aug 05 00:00:00 EDT 2019}

}

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https://doi.org/10.1021/jacs.9b06094

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Cited by: 13 works

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Figures / Tables:

Figure 1: (a) Structures of hybrid peptides 1 and 2. (b) The expected H-bonded duplex 1∙2. Labels of most hydrogens and the two aromatic residues are shown. Compound 3 corresponds to the aromatic residues of 1 and 2.

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