Packing Is a Key Selection Factor in the Evolution of Protein Hydrophobic Cores

Chen, Junmei; Stites, Wesley E.

doi:10.1021/bi011776v

Cited by 84Protein Structure and DynamicsRNA and protein synthesis mechanismsEnzyme Structure and Function

Packing Is a Key Selection Factor in the Evolution of Protein Hydrophobic Cores

Chen, Junmei, Stites, Wesley E.·2001·Biochemistry

DOI 10.1021/bi011776v

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Abstract

The energy derived from optimized van der Waals interactions in closely packed, folded proteins has been proposed to be of similar energetic magnitude to hydrophobicity in stabilizing the native state. If packing is this energetically important, it should influence the evolution of protein core sequences. To test this hypothesis, the occurrence of various amino acid side chains in the major hydrophobic core of staphylococcal nuclease and 42 homologous proteins was determined. Most such positions in this protein family are usually isoleucine, leucine, or valine. Previously we have constructed and measured the stabilities of 12 single, 44 double, 64 triple, and 32 quadruple mutants, representing all possible permutations of these three side chains at two overlapping sets of four positions in the core of staphylococcal nuclease. The stabilities and interaction energies of those mutants with various combinations of the most common, or consensus, sequence were compared to the stabilities of all other mutants. Mutants which had the consensus side-chain combinations were not necessarily the most stable, but usually were found to have the best interaction energies. In other words, these proteins were far more stable than would be predicted from simply summing the observed energetic effects of the component single mutations, apparently reflecting particularly favorable packing interactions that are possible for the most common side chains. An additional 12 mutants which tested possible alternate explanations of the results were constructed. The stabilities and interaction energies of these mutants also support the conclusion that packing is a crucial determinant guiding the sequence evolution of protein cores.

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Single sequence-based prediction considers hydrogen bonds, ion pairs, van der Waals attractions, and chiefly water-mediated hydrophobic interactions, with the hydrophobic effect driving protein folding.
“Single sequence-based prediction in solution considers forces related to hydrogen bonds, ion pairs, van der Waals attractions,139 and chiefly water-mediated hydrophobic interactions, with the hydrophobic effect the driving force for protein folding.”
From AlphaFold, Artificial Intelligence (AI), and Allostery (2022) · cites this paper as [139]

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Horovitz, A., & Fersht, A. R. (1990) · Journal of Molecular Biology · doi:10.1016/0022-2836(90)90275-q · Cited by 335 · see citing works
An analysis of packing in the protein folding problem
Richards, F. M., & Lim, W. A. (1993) · Quarterly Reviews of Biophysics · doi:10.1017/s0033583500002845 · Cited by 216 · see citing works
The human EBNA-2 coactivator p100: multidomain organization and relationship to the staphylococcal nuclease fold and to the tudor protein involved in Drosophila melanogaster development
Callebaut, I., & Mornon, J. P. (1997) · Biochemical Journal · doi:10.1042/bj3210125 · Cited by 129 · see citing works
Instrumentation for Automated Determination of Protein Stability
Stites, W. E., Byrne, M. P., Aviv, J., Kaplan, M., & Curtis, P. M. (1995) · Analytical Biochemistry · doi:10.1006/abio.1995.1259 · Cited by 24 · see citing works
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Taniuchi, H., Shi, Y. H., Miguel, G. I. S., Ferretti, J. A., Mack, J. W., Fisher, A. M., Shah, M., Schechter, A. N., & Shiloach, J. (2001) · Journal of Protein Chemistry · doi:10.1023/a:1010906929793 · Cited by 4 · see citing works

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Dill, K. A., Ozkan, S. B., Shell, M. S., & Weikl, T. R. (2008) · Annual Review of Biophysics · doi:10.1146/annurev.biophys.37.092707.153558 · Cited by 1,163 · see citing works
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Pace, C. N., Fu, H., Fryar, K. L., Landua, J. D., Trevino, S. R., Shirley, B. A., McNutt, M., Iimura, S., Gajiwala, K. S., Scholtz, J. M., et al. (2011) · Journal of Molecular Biology · doi:10.1016/j.jmb.2011.02.053 · Cited by 460 · see citing works
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Pace, C. N., Trevino, S. R., Prabhakaran, E. N., & Scholtz, J. M. (2004) · Philosophical Transactions of the Royal Society B Biological Sciences · doi:10.1098/rstb.2004.1500 · Cited by 395 · see citing works
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Chen, J., & Stites, W. E. (2004) · Journal of Molecular Biology · doi:10.1016/j.jmb.2004.09.008 · Cited by 26 · see citing works
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Talla, D., & Stites, W. E. (2008) · Proteins Structure Function and Bioinformatics · doi:10.1002/prot.22016 · Cited by 21 · see citing works
Self-citation
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Bueno, M., Campos, L. A., Estrada, J., & Sancho, J. (2006) · Protein Science · doi:10.1110/ps.062274906 · Cited by 20 · see citing works
Stability and fibril formation properties of human and fish transthyretin, and of theEscherichia colitransthyretin‐related protein
Lundberg, E., Olofsson, A., Westermark, G. T., & Sauer-Eriksson, A. E. (2009) · FEBS Journal · doi:10.1111/j.1742-4658.2009.06936.x · Cited by 18 · see citing works
An ion-responsive motif in the second transmembrane segment of rhodopsin-like receptors
Parker, M. S., Wong, Y. Y., & Parker, S. L. (2008) · Amino Acids · doi:10.1007/s00726-008-0637-6 · Cited by 18 · see citing works
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Bhardwaj, N., & Gerstein, M. (2009) · Protein Science · doi:10.1002/pro.132 · Cited by 18 · see citing works
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Font, J. S., Benito, A., Torrent, J., Lange, R., Ribó, M., & Vilanova, M. (2006) · Biological Chemistry · doi:10.1515/bc.2006.038 · Cited by 17 · see citing works
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Maturation of cytotoxic effector cells at the site of allograft rejection.
Ascher, N. L., Chen, S., Hoffman, R. P., & Simmons, R. L. (1981) · PubMed · Cited by 15 · see citing works
Physicochemical origin of high correlation between thermal stability of a protein and its packing efficiency: a theoretical study for staphylococcal nuclease mutants
Oda, K., & Kinoshita, M. (2015) · Biophysics and Physicobiology · doi:10.2142/biophysico.12.0_1 · Cited by 14 · see citing works
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Cierpicki, T., & Otlewski, J. (2002) · Journal of Molecular Biology · doi:10.1016/s0022-2836(02)00620-4 · Cited by 11 · see citing works
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Spagnolo, L., Ventura, S., & Serrano, L. (2003) · Protein Science · doi:10.1110/ps.0302603 · Cited by 8 · see citing works
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Chen, J., Lu, Z., Sakon, J., & Stites, W. E. (2004) · Biophysical Chemistry · doi:10.1016/j.bpc.2004.02.007 · Cited by 8 · see citing works
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Milán‐Garcés, E. A., Mondal, S., Udgaonkar, J. B., & Puranik, M. (2014) · Journal of Raman Spectroscopy · doi:10.1002/jrs.4558 · Cited by 8 · see citing works
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Duan, L. L., Zhu, T., Mei, Y., Zhang, Q. G., Tang, B., & Zhang, J. Z. H. (2013) · Journal of Molecular Modeling · doi:10.1007/s00894-013-1798-8 · Cited by 7 · see citing works
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Kurpiewska, K., Font, J. S., Ribó, M., Vilanova, M., & Lewiński, K. (2009) · Proteins Structure Function and Bioinformatics · doi:10.1002/prot.22480 · Cited by 7 · see citing works
Orientational distributions of contact clusters in proteins closely resemble those of an icosahedron
Feng, Y., Jernigan, R. L., & Kloczkowski, A. (2008) · Proteins Structure Function and Bioinformatics · doi:10.1002/prot.22092 · Cited by 7 · see citing works
Electrostatic interactions in the reconstitution of an SH2 domain from constituent peptide fragments
Ojennus, D. D., Lehto, S. E., & Wuttke, D. S. (2003) · Protein Science · doi:10.1110/ps.0227903 · Cited by 6 · see citing works
Construction of highly active and stable recombinant nattokinase by engineered bacteria and computational design
Wang, L.-X., Meng, J., Yu, X., Wang, J., Zhang, Y., Zhang, M., Zhang, Y., Wang, H., Feng, H., Tian, Q., et al. (2024) · Archives of Biochemistry and Biophysics · doi:10.1016/j.abb.2024.110126 · Cited by 5 · see citing works
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Xia, X., Lin, C.-T., Wang, G., & Fang, H. (2004) · Archives of Biochemistry and Biophysics · doi:10.1016/j.abb.2004.02.025 · Cited by 5 · see citing works
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Vilà, R., Benito, A., Ribó, M., & Vilanova, M. (2009) · Biopolymers · doi:10.1002/bip.21204 · Cited by 5 · see citing works
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Cheung, L. K. Y., Sanders, A. D., Pratap-Singh, A., Dee, D. R., Dupuis, J. H., Baldelli, A., & Yada, R. Y. (2023) · Elsevier eBooks · doi:10.1016/b978-0-323-98386-0.00005-1 · Cited by 4 · see citing works
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TA, N. A. K. (2015) · Journal of Glycomics & Lipidomics · doi:10.4172/2153-0637.1000128 · Cited by 4 · see citing works
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Workman, R. J., Drake, J. A., & Pettitt, B. M. (2022) · Elsevier eBooks · doi:10.1016/b978-0-323-99533-7.00015-7 · Cited by 3 · see citing works
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Pollack, J. D., Gerard, D., & Pearl, D. K. (2013) · Origins of Life and Evolution of Biospheres · doi:10.1007/s11084-013-9331-8 · Cited by 3 · see citing works
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Quirk, S., & Lieberman, R. L. (2022) · Acta Crystallographica Section F Structural Biology Communications · doi:10.1107/s2053230x22002448 · Cited by 2 · see citing works
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Davis, L. K. (2016) · arXiv (Cornell University) · doi:10.48550/arxiv.1607.03253
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Liu, J. (2013) · Scholarship@Western (Western University)
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Seeliger, D. (2008) · doi:10.53846/goediss-3458

Energetics of Side Chain Packing in Staphylococcal Nuclease Assessed by Exchange of Valines, Isoleucines, and Leucines
Holder, J. B., Bennett, A. F., Chen, J., Spencer, D. S., Byrne, M. P., & Stites, W. E. (2001) · Biochemistry · doi:10.1021/bi011267t · Cited by 41 · see citing works
Self-citation
Energetics of complementary side chain packing in a protein hydrophobic core
Kellis, J. T., Nyberg, K., & Fersht, A. R. (1989) · Biochemistry · doi:10.1021/bi00437a058 · Cited by 348 · see citing works
Proteins with simplified hydrophobic cores compared to other packing mutants
Chen, J., Lu, Z., Sakon, J., & Stites, W. E. (2004) · Biophysical Chemistry · doi:10.1016/j.bpc.2004.02.007 · Cited by 8 · see citing works
Self-citation
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Chen, J., & Stites, W. E. (2001) · Biochemistry · doi:10.1021/bi011268l · Cited by 39 · see citing works
Self-citation
The role of packing interactions in stabilizing folded proteins
Sneddon, S. F., & Tobias, D. J. (1992) · Biochemistry · doi:10.1021/bi00125a028 · Cited by 37 · see citing works

Authors: Chen, J., & Stites, W. E.
Affiliations: University of Arkansas at Fayetteville (US)
Corresponding author: Stites, Wesley E.
ORCID: Chen, Junmei
Stites, Wesley E.
Venue: Biochemistry
Publisher: American Chemical Society (ACS)
Published: 2001-11-16
Volume: 40
Issue: 50
Pages: 15280-15289
ISSN: 0006-2960 (ISSN-L)
1520-4995
DOI: 10.1021/bi011776v
OpenAlex: W1991101438
Cited by: 84
References: 5
Citations by year: 2026: 1 · 2025: 1 · 2024: 2 · 2023: 2 · 2022: 5 · 2021: 1 · 2020: 2 · 2018: 2 · 2016: 1 · 2015: 3 · 2014: 6 · 2013: 8 · 2012: 2
FWCI: 2.31
Type: journal article
Language: en
Open access: closed
Locations: Biochemistry (publishedVersion)
PubMed (publishedVersion)
Funders: National Institutes of Health (1r15gm052714-01)
National Institute of General Medical Sciences (GM52714)
National Center for Research Resources (1 P20 RR155691, P20RR015569)
Topics: Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Structure and Dynamics
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA and protein synthesis mechanisms
Physical Sciences › Materials Science › Materials Chemistry › Enzyme Structure and Function
Keywords: side-chain packing, protein evolution, staphylococcal nuclease, van der Waals interactions, protein stability, amino acid side chains, consensus sequence, interaction energy
MeSH terms: Amino Acid Sequence, Amino Acids, Enzyme Stability, Micrococcal Nuclease, Proteins, Thermodynamics, Mutagenesis, Site-Directed, Consensus Sequence, Evolution, Molecular

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Packing Is a Key Selection Factor in the Evolution of Protein Hydrophobic Cores

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