Understanding the physical properties that control protein crystallization by analysis of large-scale experimental data
The physical properties that determine the propensity of a protein to form a well-ordered crystal suitable for structure determination are poorly understood. An analysis of large-scale crystallization results generated by a structural genomics consortium highlights the importance of low-entropy surf...
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| Veröffentlicht in: | Nature biotechnology 2009-01, Vol.27 (1), p.51-57 |
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| creator | Price II, W Nicholson Chen, Yang Handelman, Samuel K Neely, Helen Manor, Philip Karlin, Richard Nair, Rajesh Liu, Jinfeng Baran, Michael Everett, John Tong, Saichiu N Forouhar, Farhad Swaminathan, Swarup S Acton, Thomas Xiao, Rong Luft, Joseph R Lauricella, Angela DeTitta, George T Rost, Burkhard Montelione, Gaetano T Hunt, John F |
| description | The physical properties that determine the propensity of a protein to form a well-ordered crystal suitable for structure determination are poorly understood. An analysis of large-scale crystallization results generated by a structural genomics consortium highlights the importance of low-entropy surface features capable of mediating protein-protein interactions.
Crystallization is the most serious bottleneck in high-throughput protein-structure determination by diffraction methods. We have used data mining of the large-scale experimental results of the Northeast Structural Genomics Consortium and experimental folding studies to characterize the biophysical properties that control protein crystallization. This analysis leads to the conclusion that crystallization propensity depends primarily on the prevalence of well-ordered surface epitopes capable of mediating interprotein interactions and is not strongly influenced by overall thermodynamic stability. We identify specific sequence features that correlate with crystallization propensity and that can be used to estimate the crystallization probability of a given construct. Analyses of entire predicted proteomes demonstrate substantial differences in the amino acid–sequence properties of human versus eubacterial proteins, which likely reflect differences in biophysical properties, including crystallization propensity. Our thermodynamic measurements do not generally support previous claims regarding correlations between sequence properties and protein stability. |
| doi_str_mv | 10.1038/nbt.1514 |
| format | Article |
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Crystallization is the most serious bottleneck in high-throughput protein-structure determination by diffraction methods. We have used data mining of the large-scale experimental results of the Northeast Structural Genomics Consortium and experimental folding studies to characterize the biophysical properties that control protein crystallization. This analysis leads to the conclusion that crystallization propensity depends primarily on the prevalence of well-ordered surface epitopes capable of mediating interprotein interactions and is not strongly influenced by overall thermodynamic stability. We identify specific sequence features that correlate with crystallization propensity and that can be used to estimate the crystallization probability of a given construct. Analyses of entire predicted proteomes demonstrate substantial differences in the amino acid–sequence properties of human versus eubacterial proteins, which likely reflect differences in biophysical properties, including crystallization propensity. Our thermodynamic measurements do not generally support previous claims regarding correlations between sequence properties and protein stability.</description><identifier>ISSN: 1087-0156</identifier><identifier>EISSN: 1546-1696</identifier><identifier>DOI: 10.1038/nbt.1514</identifier><identifier>PMID: 19079241</identifier><language>eng</language><publisher>New York: Nature Publishing Group US</publisher><subject>Agriculture ; Algorithms ; Amino acids ; analysis ; Animals ; BASIC BIOLOGICAL SCIENCES ; Bioinformatics ; Biomedical and Life Sciences ; Biomedical Engineering/Biotechnology ; Biomedicine ; Biophysics - methods ; Biotechnology ; Computational Biology - methods ; CONTROL ; CORRELATIONS ; CRYSTALLIZATION ; DATA ; Data mining ; DIFFRACTION METHODS ; Entropy ; Epitopes - chemistry ; EXPERIMENTAL DATA ; GENERAL AND MISCELLANEOUS//MATHEMATICS, COMPUTING, AND INFORMATION SCIENCE ; Genomics ; HUMAN POPULATIONS ; Humans ; INTERACTIONS ; Life Sciences ; MINING ; Models, Statistical ; national synchrotron light source ; PHYSICAL PROPERTIES ; Physiological aspects ; PROBABILITY ; Properties ; Protein Folding ; PROTEIN STRUCTURE ; PROTEINS ; Proteins - chemistry ; STABILITY ; Structure ; SUPPORTS ; Surface Properties ; SURFACES ; THERMODYNAMICS</subject><ispartof>Nature biotechnology, 2009-01, Vol.27 (1), p.51-57</ispartof><rights>Springer Nature America, Inc. 2008</rights><rights>COPYRIGHT 2009 Nature Publishing Group</rights><rights>Copyright Nature Publishing Group Jan 2009</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c540t-1036c4dd7e32aa7f5ebd020e08473350c51d4cb62859c56e39b59be4ec93052c3</citedby><cites>FETCH-LOGICAL-c540t-1036c4dd7e32aa7f5ebd020e08473350c51d4cb62859c56e39b59be4ec93052c3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://link.springer.com/content/pdf/10.1038/nbt.1514$$EPDF$$P50$$Gspringer$$H</linktopdf><linktohtml>$$Uhttps://link.springer.com/10.1038/nbt.1514$$EHTML$$P50$$Gspringer$$H</linktohtml><link.rule.ids>230,314,776,780,881,27901,27902,41464,42533,51294</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/19079241$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink><backlink>$$Uhttps://www.osti.gov/biblio/980665$$D View this record in Osti.gov$$Hfree_for_read</backlink></links><search><creatorcontrib>Price II, W Nicholson</creatorcontrib><creatorcontrib>Chen, Yang</creatorcontrib><creatorcontrib>Handelman, Samuel K</creatorcontrib><creatorcontrib>Neely, Helen</creatorcontrib><creatorcontrib>Manor, Philip</creatorcontrib><creatorcontrib>Karlin, Richard</creatorcontrib><creatorcontrib>Nair, Rajesh</creatorcontrib><creatorcontrib>Liu, Jinfeng</creatorcontrib><creatorcontrib>Baran, Michael</creatorcontrib><creatorcontrib>Everett, John</creatorcontrib><creatorcontrib>Tong, Saichiu N</creatorcontrib><creatorcontrib>Forouhar, Farhad</creatorcontrib><creatorcontrib>Swaminathan, Swarup S</creatorcontrib><creatorcontrib>Acton, Thomas</creatorcontrib><creatorcontrib>Xiao, Rong</creatorcontrib><creatorcontrib>Luft, Joseph R</creatorcontrib><creatorcontrib>Lauricella, Angela</creatorcontrib><creatorcontrib>DeTitta, George T</creatorcontrib><creatorcontrib>Rost, Burkhard</creatorcontrib><creatorcontrib>Montelione, Gaetano T</creatorcontrib><creatorcontrib>Hunt, John F</creatorcontrib><creatorcontrib>Brookhaven National Laboratory (BNL) National Synchrotron Light Source</creatorcontrib><title>Understanding the physical properties that control protein crystallization by analysis of large-scale experimental data</title><title>Nature biotechnology</title><addtitle>Nat Biotechnol</addtitle><addtitle>Nat Biotechnol</addtitle><description>The physical properties that determine the propensity of a protein to form a well-ordered crystal suitable for structure determination are poorly understood. An analysis of large-scale crystallization results generated by a structural genomics consortium highlights the importance of low-entropy surface features capable of mediating protein-protein interactions.
Crystallization is the most serious bottleneck in high-throughput protein-structure determination by diffraction methods. We have used data mining of the large-scale experimental results of the Northeast Structural Genomics Consortium and experimental folding studies to characterize the biophysical properties that control protein crystallization. This analysis leads to the conclusion that crystallization propensity depends primarily on the prevalence of well-ordered surface epitopes capable of mediating interprotein interactions and is not strongly influenced by overall thermodynamic stability. We identify specific sequence features that correlate with crystallization propensity and that can be used to estimate the crystallization probability of a given construct. Analyses of entire predicted proteomes demonstrate substantial differences in the amino acid–sequence properties of human versus eubacterial proteins, which likely reflect differences in biophysical properties, including crystallization propensity. Our thermodynamic measurements do not generally support previous claims regarding correlations between sequence properties and protein stability.</description><subject>Agriculture</subject><subject>Algorithms</subject><subject>Amino acids</subject><subject>analysis</subject><subject>Animals</subject><subject>BASIC BIOLOGICAL SCIENCES</subject><subject>Bioinformatics</subject><subject>Biomedical and Life Sciences</subject><subject>Biomedical Engineering/Biotechnology</subject><subject>Biomedicine</subject><subject>Biophysics - methods</subject><subject>Biotechnology</subject><subject>Computational Biology - methods</subject><subject>CONTROL</subject><subject>CORRELATIONS</subject><subject>CRYSTALLIZATION</subject><subject>DATA</subject><subject>Data mining</subject><subject>DIFFRACTION METHODS</subject><subject>Entropy</subject><subject>Epitopes - chemistry</subject><subject>EXPERIMENTAL DATA</subject><subject>GENERAL AND MISCELLANEOUS//MATHEMATICS, COMPUTING, AND INFORMATION 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biotechnology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Price II, W Nicholson</au><au>Chen, Yang</au><au>Handelman, Samuel K</au><au>Neely, Helen</au><au>Manor, Philip</au><au>Karlin, Richard</au><au>Nair, Rajesh</au><au>Liu, Jinfeng</au><au>Baran, Michael</au><au>Everett, John</au><au>Tong, Saichiu N</au><au>Forouhar, Farhad</au><au>Swaminathan, Swarup S</au><au>Acton, Thomas</au><au>Xiao, Rong</au><au>Luft, Joseph R</au><au>Lauricella, Angela</au><au>DeTitta, George T</au><au>Rost, Burkhard</au><au>Montelione, Gaetano T</au><au>Hunt, John F</au><aucorp>Brookhaven National Laboratory (BNL) National Synchrotron Light Source</aucorp><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Understanding the physical properties that control protein crystallization by analysis of large-scale experimental data</atitle><jtitle>Nature biotechnology</jtitle><stitle>Nat Biotechnol</stitle><addtitle>Nat Biotechnol</addtitle><date>2009-01-01</date><risdate>2009</risdate><volume>27</volume><issue>1</issue><spage>51</spage><epage>57</epage><pages>51-57</pages><issn>1087-0156</issn><eissn>1546-1696</eissn><abstract>The physical properties that determine the propensity of a protein to form a well-ordered crystal suitable for structure determination are poorly understood. An analysis of large-scale crystallization results generated by a structural genomics consortium highlights the importance of low-entropy surface features capable of mediating protein-protein interactions.
Crystallization is the most serious bottleneck in high-throughput protein-structure determination by diffraction methods. We have used data mining of the large-scale experimental results of the Northeast Structural Genomics Consortium and experimental folding studies to characterize the biophysical properties that control protein crystallization. This analysis leads to the conclusion that crystallization propensity depends primarily on the prevalence of well-ordered surface epitopes capable of mediating interprotein interactions and is not strongly influenced by overall thermodynamic stability. We identify specific sequence features that correlate with crystallization propensity and that can be used to estimate the crystallization probability of a given construct. Analyses of entire predicted proteomes demonstrate substantial differences in the amino acid–sequence properties of human versus eubacterial proteins, which likely reflect differences in biophysical properties, including crystallization propensity. Our thermodynamic measurements do not generally support previous claims regarding correlations between sequence properties and protein stability.</abstract><cop>New York</cop><pub>Nature Publishing Group US</pub><pmid>19079241</pmid><doi>10.1038/nbt.1514</doi><tpages>7</tpages><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 1087-0156 |
| ispartof | Nature biotechnology, 2009-01, Vol.27 (1), p.51-57 |
| issn | 1087-0156 1546-1696 |
| language | eng |
| recordid | cdi_osti_scitechconnect_980665 |
| source | MEDLINE; SpringerLink Journals; Nature Journals Online |
| subjects | Agriculture Algorithms Amino acids analysis Animals BASIC BIOLOGICAL SCIENCES Bioinformatics Biomedical and Life Sciences Biomedical Engineering/Biotechnology Biomedicine Biophysics - methods Biotechnology Computational Biology - methods CONTROL CORRELATIONS CRYSTALLIZATION DATA Data mining DIFFRACTION METHODS Entropy Epitopes - chemistry EXPERIMENTAL DATA GENERAL AND MISCELLANEOUS//MATHEMATICS, COMPUTING, AND INFORMATION SCIENCE Genomics HUMAN POPULATIONS Humans INTERACTIONS Life Sciences MINING Models, Statistical national synchrotron light source PHYSICAL PROPERTIES Physiological aspects PROBABILITY Properties Protein Folding PROTEIN STRUCTURE PROTEINS Proteins - chemistry STABILITY Structure SUPPORTS Surface Properties SURFACES THERMODYNAMICS |
| title | Understanding the physical properties that control protein crystallization by analysis of large-scale experimental data |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-02-13T05%3A56%3A02IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-gale_osti_&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Understanding%20the%20physical%20properties%20that%20control%20protein%20crystallization%20by%20analysis%20of%20large-scale%20experimental%20data&rft.jtitle=Nature%20biotechnology&rft.au=Price%20II,%20W%20Nicholson&rft.aucorp=Brookhaven%20National%20Laboratory%20(BNL)%20National%20Synchrotron%20Light%20Source&rft.date=2009-01-01&rft.volume=27&rft.issue=1&rft.spage=51&rft.epage=57&rft.pages=51-57&rft.issn=1087-0156&rft.eissn=1546-1696&rft_id=info:doi/10.1038/nbt.1514&rft_dat=%3Cgale_osti_%3EA197491103%3C/gale_osti_%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=222290663&rft_id=info:pmid/19079241&rft_galeid=A197491103&rfr_iscdi=true |