The DOI matches its Crossref record; 46 of the 46 references it cites were found in a registry or an index.
Antibody evolution constrains conformational heterogeneity by tailoring protein dynamics
Open accessAbstract
The evolution of proteins with novel function is thought to start from precursor proteins that are conformationally heterogeneous. The corresponding genes may be duplicated and then mutated to select and optimize a specific conformation. However, testing this idea has been difficult because of the challenge of quantifying protein flexibility and conformational heterogeneity as a function of evolution. Here, we report the characterization of protein heterogeneity and dynamics as a function of evolution for the antifluorescein antibody 4-4-20. Using nonlinear laser spectroscopy, surface plasmon resonance, and molecular dynamics simulations, we demonstrate that evolution localized the Ab-combining site from a heterogeneous ensemble of conformations to a single conformation by introducing mutations that act cooperatively and over significant distances to rigidify the protein. This study demonstrates how protein dynamics may be tailored by evolution and has important implications for our understanding of how novel protein functions are evolved.
Overview
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
In the citing paper
“Controlled evolution of the antifluorescein antibody 4–4-20 localized the Ab-combining site from a heterogeneous ensemble of conformations to a single conformation by introducing mutations that act cooperatively and over significant distances to rigidify the protein.519”
From Protein Ensembles: How Does Nature Harness Thermodynamic Fluctuations for Life? The Diverse Functional Roles of Conformational Ensembles in the Cell (2016) · cites this paper as [519]
In the citing paper
“Antibody evolution may constrain conformational heterogeneity by tailoring protein dynamics.519”
From Protein Ensembles: How Does Nature Harness Thermodynamic Fluctuations for Life? The Diverse Functional Roles of Conformational Ensembles in the Cell (2016) · cites this paper as [519]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Citations
Cites
Comparison of simple potential functions for simulating liquid water
Jorgensen, W. L., Chandrasekhar, J., Madura, J., Impey, R., & Klein, M. (1983) · The Journal of Chemical Physics · doi:10.1063/1.445869 · Cited by 38,397
Ryckaert, J.-P., Ciccotti, G., & Berendsen, H. J. C. (1977) · Journal of Computational Physics · doi:10.1016/0021-9991(77)90098-5 · Cited by 21,430
Principles of Nonlinear Optical Spectroscopy
Mukamel, S. (1995) · Cited by 4,640
Swope, W. C., Andersen, H. C., Berens, P. H., & Wilson, K. R. (1982) · The Journal of Chemical Physics · doi:10.1063/1.442716 · Cited by 4,068
The Energy Landscapes and Motions of Proteins
Frauenfelder, H., Sligar, S. G., & Wolynes, P. G. (1991) · Science · doi:10.1126/science.1749933 · Cited by 3,250
Encyclopedia of Computational Chemistry
(2003) · Wiley eBooks · doi:10.1002/0470845015 · Cited by 2,757
Encyclopedia of Computational Chemistry
Horn, A. H. C., & Lanig, H. (1999) · Journal of Molecular Modeling · doi:10.1007/s0089490050141 · Cited by 2,524
Application of a Theory of Enzyme Specificity to Protein Synthesis.
Koshland, D. (1958) · Proceedings of the National Academy of Sciences of the United States of America · doi:10.1073/pnas.44.2.98 · Cited by 2,140
Subpicosecond Measurements of Polar Solvation Dynamics: Coumarin 153 Revisited
Horng, M. L., Gardecki, J. A., Papazyan, A., & Maroncelli, M. (1995) · The Journal of Physical Chemistry · doi:10.1021/j100048a004 · Cited by 2,091
Femtosecond solvation dynamics of water
Jimenez, R., Fleming, G. R., Kumar, P. V., & Maroncelli, M. (1994) · Nature · doi:10.1038/369471a0 · Cited by 1,271
A very high level of crossreactivity is an essential feature of the T-cell receptor.
Mason, D. (1998) · Immunology today (Amsterdam. Regular ed.) · doi:10.1016/s0167-5699(98)01299-7 · Cited by 1,067
Feig, M., Karanicolas, J., & Brooks, C. L. (2004) · Journal of Molecular Graphics and Modelling · doi:10.1016/j.jmgm.2003.12.005 · Cited by 861
Self-citationThe 'evolvability' of promiscuous protein functions
Aharoni, A., Gaidukov, L., Khersonsky, O., Gould, S. M., Roodveldt, C., & Tawfik, D. S. (2004) · Nature Genetics · doi:10.1038/ng1482 · Cited by 833
How Soft Is a Protein? A Protein Dynamics Force Constant Measured by Neutron Scattering
Zaccaı̈, G. (2000) · Science · doi:10.1126/science.288.5471.1604 · Cited by 742
Catalytic promiscuity and the evolution of new enzymatic activities
O’Brien, P., & Herschlag, D. (1999) · Chemistry & Biology · doi:10.1016/s1074-5521(99)80033-7 · Cited by 731
Antibody Multispecificity Mediated by Conformational Diversity
James, L. C., Roversi, P., & Tawfik, D. S. (2003) · Science · doi:10.1126/science.1079731 · Cited by 719
Fleming, G. R., & Cho, M. (1996) · Annual Review of Physical Chemistry · doi:10.1146/annurev.physchem.47.1.109 · Cited by 680
Conformational diversity and protein evolution – a 60-year-old hypothesis revisited
James, L. C., & Tawfik, D. S. (2003) · Trends in Biochemical Sciences · doi:10.1016/s0968-0004(03)00135-x · Cited by 579
Rongvaux, A., Shea, R. J., Mulks, M. H., Gigot, D., Urbain, J., Léo, O., & Andris, F. (2002) · European Journal of Immunology · doi:10.1002/1521-4141(200211)32:11 · Cited by 551
Structural Insights into the Evolution of an Antibody Combining Site
Wedemayer, G. J., Patten, P. A., Wang, L. H., Schultz, P. G., & Stevens, R. C. (1997) · Science · doi:10.1126/science.276.5319.1665 · Cited by 550
Enzymes with extra talents: moonlighting functions and catalytic promiscuity
Copley, S. D. (2003) · Current Opinion in Chemical Biology · doi:10.1016/s1367-5931(03)00032-2 · Cited by 518
Intrinsic and Extrinsic Factors in Protein Antigenic Structure
Berzofsky, J. A. (1985) · Science · doi:10.1126/science.2410982 · Cited by 482
Multiple diverse ligands binding at a single protein site: A matter of pre‐existing populations
Ma, B., Shatsky, M., Wolfson, H. J., & Nussinov, R. (2002) · Protein Science · doi:10.1110/ps.21302 · Cited by 420
Polyreactivity of antibody molecules
Notkins, A. L. (2004) · Trends in Immunology · doi:10.1016/j.it.2004.02.004 · Cited by 281
Conformational isomerism and the diversity of antibodies.
Foote, J., & Milstein, C. (1994) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.91.22.10370 · Cited by 264
Molecular recognition in antibody-antigen complexes
Sundberg, E. J., & Mariuzza, R. A. (2002) · Advances in protein chemistry · doi:10.1016/s0065-3233(02)61004-6 · Cited by 255
The Immunological Evolution of Catalysis
Patten, P. A., Gray, N. S., Yang, P. L., Marks, C. B., Wedemayer, G. J., Boniface, J. J., Stevens, R. C., & Schultz, P. G. (1996) · Science · doi:10.1126/science.271.5252.1086 · Cited by 227
Steinbach, P. J., Ionescu, R. M., & Matthews, C. R. (2002) · Biophysical Journal · doi:10.1016/s0006-3495(02)75570-7 · Cited by 194
Manivel, V., Sahoo, N., Salunke, D. M., & Rao, K. V. S. (2000) · Immunity · doi:10.1016/s1074-7613(00)00061-3 · Cited by 189
Dielectric relaxation in a protein matrix
Pierce, D. W., & Boxer, S. G. (1992) · The Journal of Physical Chemistry · doi:10.1021/j100192a069 · Cited by 140
Self-citationA two‐phase model of B‐cell activation
Baumgarth, N. (2000) · Immunological Reviews · doi:10.1034/j.1600-065x.2000.00606.x · Cited by 135
Proteins in action: the physics of structural fluctuations and conformational changes
Parak, F. (2003) · Current Opinion in Structural Biology · doi:10.1016/j.sbi.2003.09.004 · Cited by 123
Flexibility and molecular recognition in the immune system
Jimenez, R., Salazar, G. T., Baldridge, K. K., & Romesberg, F. E. (2002) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.262411399 · Cited by 122
Self-citationStructural Plasticity and the Evolution of Antibody Affinity and Specificity
Yin, J., Beuscher, A. E., Andryski, S. E., Stevens, R. C., & Schultz, P. G. (2003) · Journal of Molecular Biology · doi:10.1016/s0022-2836(03)00631-4 · Cited by 117
Preferential autoantibody reactivity of the preimmune B cell repertoire in normal mice.
Souroujon, M. C., White‐Scharf, M. E., André-Schwartz, J., Gefter, M. L., & Schwartz, R. S. (1988) · The Journal of Immunology · doi:10.4049/jimmunol.140.12.4173 · Cited by 110
Protein dynamics and the immunological evolution of molecular recognition
Jimenez, R., Salazar, G. T., Yin, J., Joo, T., & Romesberg, F. E. (2004) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0305745101 · Cited by 100
Self-citationExpression studies of catalytic antibodies.
Ulrich, H. D., Patten, P. A., Yang, P. L., Romesberg, F. E., & Schultz, P. G. (1995) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.92.25.11907 · Cited by 81
Self-citation1.85 Å structure of anti-fluorescein 4-4-20 Fab
Whitlow, M. D., Howard, A. J., Wood, J. F., Voss, E. W., & Hardman, K. D. (1995) · Protein Engineering Design and Selection · doi:10.1093/protein/8.8.749 · Cited by 75
A Comparative Analysis of the Immunological Evolution of Antibody 28B4
Yin, J., Mundorff, E. C., Yang, P. L., Wendt, K. U., Hanway, D., Stevens, R. C., & Schultz, P. G. (2001) · Biochemistry · doi:10.1021/bi010536c · Cited by 73
Thermodynamic and kinetic aspects of antibody evolution during the immune response to hapten
Sagawa, T., Oda, M., Ishimura, M., Furukawa, K., & Azuma, T. (2003) · Molecular Immunology · doi:10.1016/s0161-5890(02)00282-1 · Cited by 63
Ig repertoire of human polyspecific antibodies and B cell ontogeny
Guigou, V., Guilbert, B., Moinier, D., Tonnelle, C., Boubli, L., Avraméas, S., Fougereau, M., & Fumoux, F. (1991) · The Journal of Immunology · doi:10.4049/jimmunol.146.4.1368 · Cited by 55
Flexibility of an Antibody Binding Site Measured with Photon Echo Spectroscopy
Jimenez, R., Case, D. A., & Romesberg, F. E. (2002) · The Journal of Physical Chemistry B · doi:10.1021/jp013110g · Cited by 41
Self-citationEvolutionary Chemistry: Getting There from Here
Joyce, G. F. (1997) · Science · doi:10.1126/science.276.5319.1658 · Cited by 34
McAnaney, T. B., Shi, X., Abbyad, P., Jung, H., Remington, S. J., & Boxer, S. G. (2005) · Biochemistry · doi:10.1021/bi050132a · Cited by 34
Self-citationCorrelation between evolutionary structural development and protein folding
Nagao, C., Terada, T. P., Yomo, T., & Sasai, M. (2005) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0509163102 · Cited by 16
Probing the human natural autoantibody repertoire using an immunoscreening approach
Comtesse, N., Heckel, D., Maldener, E., Glass, B., & Meese, E. U. (2000) · Clinical & Experimental Immunology · doi:10.1046/j.1365-2249.2000.01322.x · Cited by 15
Research works printed but not linked: 1
- PD Hodgkin Immunologist 6, 223–226 (1998).
Cited by
Sorted by citations
Protein promiscuity and its implications for biotechnology
Nobeli, I., Favia, A. D., & Thornton, J. M. (2009) · Nature Biotechnology · doi:10.1038/nbt1519 · Cited by 508
Wei, G., Xi, W., Nussinov, R., & Ma, B. (2016) · Chemical Reviews · doi:10.1021/acs.chemrev.5b00562 · Cited by 436
Computer-aided antibody design
Kuroda, D., Shirai, H., Jacobson, M. P., & Nakamura, H. (2012) · Protein Engineering Design and Selection · doi:10.1093/protein/gzs024 · Cited by 225
Almagro, J. C., & Fransson, J. (2008) · PubMed · doi:10.2741/2786 · Cited by 223
Nitrile groups as vibrational probes of biomolecular structure and dynamics: an overview
Lindquist, B. A., Furse, K. E., & Corcelli, S. A. (2009) · Physical Chemistry Chemical Physics · doi:10.1039/b908588b · Cited by 171
Metadata
- Authors
- Zimmermann, J., Oakman, E. L., Thorpe, I. F., Shi, X., Abbyad, P., Brooks, C. L., Boxer, S. G., & Romesberg, F. E.
- Affiliations
- Departments of *Chemistry and
- University of California San Diego (US)
- Scripps Research Institute (US)
- Stanford University (US)
- Venue
- Proceedings of the National Academy of Sciences
- Publisher
- National Academy of Sciences
- Published
- 2006-09-12
- Volume
- 103
- Issue
- 37
- Pages
- 13722-13727
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- PMC
- PMC1564241
- OpenAlex
- W2132524280
- Cited by
- 116
- References
- 46
- Citations by year
- 2025: 1 · 2024: 3 · 2023: 1 · 2022: 10 · 2021: 3 · 2020: 4 · 2019: 6 · 2018: 7 · 2017: 3 · 2016: 4 · 2015: 8 · 2014: 8 · 2013: 6 · 2012: 11
- FWCI
- 3.54
- Type
- journal article
- Language
- en
- Open access
- green
- europepmc.org
- Locations
- Proceedings of the National Academy of Sciences (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Structure and Dynamics
- Life Sciences › Immunology and Microbiology › Immunology › Monoclonal and Polyclonal Antibodies Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Evolution and Genetic Dynamics
- Keywords
- antibody evolution, conformational heterogeneity, protein dynamics, combining site, protein flexibility
- MeSH terms
- Animals, Antibodies, Humans, Immunoglobulin Fab Fragments, Mutation, Protein Conformation, Proteins, Evolution, Molecular, Fluorescein, Surface Plasmon Resonance
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
