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Title: Perplexing cooperative folding and stability of a low-sequence complexity, polyproline 2 protein lacking a hydrophobic core

Abstract

The burial of hydrophobic side chains in a protein core generally is thought to be the major ingredient for stable, cooperative folding. Here, we show that, for the snow flea antifreeze protein (sfAFP), stability and cooperativity can occur without a hydrophobic core, and without α-helices or β-sheets. We report sfAFP has low sequence complexity with 46% glycine and an interior filled only with backbone H-bonds between six polyproline 2 (PP2) helices. However, the protein folds in a kinetically two-state manner and is moderately stable at room temperature. We believe that a major part of the stability arises from the unusual match between residue-level PP2 dihedral angle bias in the unfolded state and PP2 helical structure in the native state. Additional stabilizing factors that compensate for the dearth of hydrophobic burial include shorter and stronger H-bonds, and increased entropy in the folded state. These results extend our understanding of the origins of cooperativity and stability in protein folding, including the balance between solvent and polypeptide chain entropies.

Authors:
 [1];  [1];  [1];  [1];  [1];  [1];  [1];  [1]
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  1. Univ. of Chicago, IL (United States)
Publication Date:
Research Org.:
Argonne National Laboratory (ANL), Argonne, IL (United States). Advanced Photon Source (APS)
Sponsoring Org.:
National Institutes of Health (NIH); National Science Foundation (NSF); USDOE Office of Science (SC), Basic Energy Sciences (BES). Scientific User Facilities Division; National Research Foundation of Korea (NRF)
OSTI Identifier:
1352210
Grant/Contract Number:  
R01 GM055694; GM-072558; CHE-1363012; AC02-06CH11357; 9 P41 GM103622; 1S10OD018090-01; 2011-0000041
Resource Type:
Accepted Manuscript
Journal Name:
Proceedings of the National Academy of Sciences of the United States of America
Additional Journal Information:
Journal Volume: 114; Journal Issue: 9; Journal ID: ISSN 0027-8424
Publisher:
National Academy of Sciences
Country of Publication:
United States
Language:
ENGLISH
Subject:
37 INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CHEMISTRY; 59 BASIC BIOLOGICAL SCIENCES; protein folding; cooperativity; kinetics; PP2; hydrogen bonding

Citation Formats

Gates, Zachary P., Baxa, Michael C., Yu, Wookyung, Riback, Joshua A., Li, Hui, Roux, Benoît, Kent, Stephen B. H., and Sosnick, Tobin R. Perplexing cooperative folding and stability of a low-sequence complexity, polyproline 2 protein lacking a hydrophobic core. United States: N. p., 2017. Web. doi:10.1073/pnas.1609579114.
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Gates, Zachary P., Baxa, Michael C., Yu, Wookyung, Riback, Joshua A., Li, Hui, Roux, Benoît, Kent, Stephen B. H., & Sosnick, Tobin R. Perplexing cooperative folding and stability of a low-sequence complexity, polyproline 2 protein lacking a hydrophobic core. United States. https://doi.org/10.1073/pnas.1609579114
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Gates, Zachary P., Baxa, Michael C., Yu, Wookyung, Riback, Joshua A., Li, Hui, Roux, Benoît, Kent, Stephen B. H., and Sosnick, Tobin R. Mon . "Perplexing cooperative folding and stability of a low-sequence complexity, polyproline 2 protein lacking a hydrophobic core". United States. https://doi.org/10.1073/pnas.1609579114. https://www.osti.gov/servlets/purl/1352210.
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@article{osti_1352210,
title = {Perplexing cooperative folding and stability of a low-sequence complexity, polyproline 2 protein lacking a hydrophobic core},
author = {Gates, Zachary P. and Baxa, Michael C. and Yu, Wookyung and Riback, Joshua A. and Li, Hui and Roux, Benoît and Kent, Stephen B. H. and Sosnick, Tobin R.},
abstractNote = {The burial of hydrophobic side chains in a protein core generally is thought to be the major ingredient for stable, cooperative folding. Here, we show that, for the snow flea antifreeze protein (sfAFP), stability and cooperativity can occur without a hydrophobic core, and without α-helices or β-sheets. We report sfAFP has low sequence complexity with 46% glycine and an interior filled only with backbone H-bonds between six polyproline 2 (PP2) helices. However, the protein folds in a kinetically two-state manner and is moderately stable at room temperature. We believe that a major part of the stability arises from the unusual match between residue-level PP2 dihedral angle bias in the unfolded state and PP2 helical structure in the native state. Additional stabilizing factors that compensate for the dearth of hydrophobic burial include shorter and stronger H-bonds, and increased entropy in the folded state. These results extend our understanding of the origins of cooperativity and stability in protein folding, including the balance between solvent and polypeptide chain entropies.},
doi = {10.1073/pnas.1609579114},
journal = {Proceedings of the National Academy of Sciences of the United States of America},
number = 9,
volume = 114,
place = {United States},
year = {Mon Feb 13 00:00:00 EST 2017},
month = {Mon Feb 13 00:00:00 EST 2017}
}
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https://doi.org/10.1073/pnas.1609579114
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