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  • 1
    Publication Date: 2014-05-30
    Description: The self-assembly of proteins into highly ordered nanoscale architectures is a hallmark of biological systems. The sophisticated functions of these molecular machines have inspired the development of methods to engineer self-assembling protein nanostructures; however, the design of multi-component protein nanomaterials with high accuracy remains an outstanding challenge. Here we report a computational method for designing protein nanomaterials in which multiple copies of two distinct subunits co-assemble into a specific architecture. We use the method to design five 24-subunit cage-like protein nanomaterials in two distinct symmetric architectures and experimentally demonstrate that their structures are in close agreement with the computational design models. The accuracy of the method and the number and variety of two-component materials that it makes accessible suggest a route to the construction of functional protein nanomaterials tailored to specific applications.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4137318/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4137318/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉King, Neil P -- Bale, Jacob B -- Sheffler, William -- McNamara, Dan E -- Gonen, Shane -- Gonen, Tamir -- Yeates, Todd O -- Baker, David -- T32 GM067555/GM/NIGMS NIH HHS/ -- T32GM067555/GM/NIGMS NIH HHS/ -- Howard Hughes Medical Institute/ -- England -- Nature. 2014 Jun 5;510(7503):103-8. doi: 10.1038/nature13404. Epub 2014 May 25.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉1] Department of Biochemistry, University of Washington, Seattle, Washington 98195, USA [2] Institute for Protein Design, University of Washington, Seattle, Washington 98195, USA [3]. ; 1] Department of Biochemistry, University of Washington, Seattle, Washington 98195, USA [2] Graduate Program in Molecular and Cellular Biology, University of Washington, Seattle, Washington 98195, USA [3]. ; 1] Department of Biochemistry, University of Washington, Seattle, Washington 98195, USA [2]. ; UCLA Department of Chemistry and Biochemistry, Los Angeles, California 90095, USA. ; 1] Department of Biochemistry, University of Washington, Seattle, Washington 98195, USA [2] Janelia Farm Research Campus, Howard Hughes Medical Institute, 19700 Helix Drive, Ashburn, Virginia 20147, USA. ; Janelia Farm Research Campus, Howard Hughes Medical Institute, 19700 Helix Drive, Ashburn, Virginia 20147, USA. ; 1] UCLA Department of Chemistry and Biochemistry, Los Angeles, California 90095, USA [2] UCLA-DOE Institute for Genomics and Proteomics, Los Angeles, California 90095, USA [3] UCLA Molecular Biology Institute, Los Angeles, California 90095, USA. ; 1] Department of Biochemistry, University of Washington, Seattle, Washington 98195, USA [2] Institute for Protein Design, University of Washington, Seattle, Washington 98195, USA [3] Howard Hughes Medical Institute, University of Washington, Seattle, Washington 98195, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24870237" target="_blank"〉PubMed〈/a〉
    Keywords: Computer Simulation ; Crystallography, X-Ray ; Drug Design ; Models, Molecular ; Nanostructures/*chemistry/ultrastructure ; Protein Subunits/chemistry ; Proteins/*chemistry/ultrastructure
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
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  • 2
    Publication Date: 2010-01-02
    Description: Many bacterial cells contain proteinaceous microcompartments that act as simple organelles by sequestering specific metabolic processes involving volatile or toxic metabolites. Here we report the three-dimensional (3D) crystal structures, with resolutions between 1.65 and 2.5 angstroms, of the four homologous proteins (EutS, EutL, EutK, and EutM) that are thought to be the major shell constituents of a functionally complex ethanolamine utilization (Eut) microcompartment. The Eut microcompartment is used to sequester the metabolism of ethanolamine in bacteria such as Escherichia coli and Salmonella enterica. The four Eut shell proteins share an overall similar 3D fold, but they have distinguishing structural features that help explain the specific roles they play in the microcompartment. For example, EutL undergoes a conformational change that is probably involved in gating molecular transport through shell protein pores, whereas structural evidence suggests that EutK might bind a nucleic acid component. Together these structures give mechanistic insight into bacterial microcompartments.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Tanaka, Shiho -- Sawaya, Michael R -- Yeates, Todd O -- Howard Hughes Medical Institute/ -- New York, N.Y. -- Science. 2010 Jan 1;327(5961):81-4. doi: 10.1126/science.1179513.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Chemistry and Biochemistry, University of California Los Angeles, 611 Charles Young Drive East, Los Angeles, CA 90095, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20044574" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; *Cell Compartmentation ; Crystallography, X-Ray ; Escherichia coli K12/*chemistry/*metabolism/ultrastructure ; Escherichia coli Proteins/*chemistry/metabolism ; Ethanolamine/*metabolism ; Metabolic Networks and Pathways ; Models, Molecular ; Molecular Sequence Data ; Polyproteins/*chemistry/metabolism ; Protein Conformation ; Protein Folding ; Protein Structure, Quaternary ; Protein Structure, Tertiary ; Protein Subunits/chemistry/metabolism
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 3
    Publication Date: 2012-06-02
    Description: Designing protein molecules that will assemble into various kinds of ordered materials represents an important challenge in nanotechnology. We report the crystal structure of a 12-subunit protein cage that self-assembles by design to form a tetrahedral structure roughly 16 nanometers in diameter. The strategy of fusing together oligomeric protein domains can be generalized to produce other kinds of cages or extended materials.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Lai, Yen-Ting -- Cascio, Duilio -- Yeates, Todd O -- New York, N.Y. -- Science. 2012 Jun 1;336(6085):1129. doi: 10.1126/science.1219351.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉University of California Los Angeles Biomedical Engineering Interdepartmental Program, Los Angeles, CA 90095, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/22654051" target="_blank"〉PubMed〈/a〉
    Keywords: Crystallography, X-Ray ; Models, Molecular ; Peroxidases/*chemistry ; Protein Conformation ; *Protein Engineering ; Protein Multimerization ; Protein Structure, Secondary ; Protein Structure, Tertiary ; Protein Subunits/chemistry ; Proteins/*chemistry ; Viral Matrix Proteins/*chemistry
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 4
    Publication Date: 2012-06-02
    Description: We describe a general computational method for designing proteins that self-assemble to a desired symmetric architecture. Protein building blocks are docked together symmetrically to identify complementary packing arrangements, and low-energy protein-protein interfaces are then designed between the building blocks in order to drive self-assembly. We used trimeric protein building blocks to design a 24-subunit, 13-nm diameter complex with octahedral symmetry and a 12-subunit, 11-nm diameter complex with tetrahedral symmetry. The designed proteins assembled to the desired oligomeric states in solution, and the crystal structures of the complexes revealed that the resulting materials closely match the design models. The method can be used to design a wide variety of self-assembling protein nanomaterials.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4138882/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4138882/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉King, Neil P -- Sheffler, William -- Sawaya, Michael R -- Vollmar, Breanna S -- Sumida, John P -- Andre, Ingemar -- Gonen, Tamir -- Yeates, Todd O -- Baker, David -- RR-15301/RR/NCRR NIH HHS/ -- Howard Hughes Medical Institute/ -- New York, N.Y. -- Science. 2012 Jun 1;336(6085):1171-4. doi: 10.1126/science.1219364.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Biochemistry, University of Washington, Seattle, WA 98195, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/22654060" target="_blank"〉PubMed〈/a〉
    Keywords: Chromatography, Gel ; Cloning, Molecular ; Computational Biology ; Computer Simulation ; Crystallography, X-Ray ; Escherichia coli/genetics/metabolism ; Hydrogen Bonding ; Microscopy, Electron ; Models, Molecular ; Molecular Weight ; Mutation ; *Nanostructures ; *Protein Engineering ; *Protein Multimerization ; Protein Structure, Secondary ; Protein Subunits/*chemistry/genetics ; Proteins/*chemistry/genetics
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 5
    Electronic Resource
    Electronic Resource
    [S.l.] : International Union of Crystallography (IUCr)
    Acta crystallographica 43 (1987), S. 30-36 
    ISSN: 1600-5724
    Source: Crystallography Journals Online : IUCR Backfile Archive 1948-2001
    Topics: Chemistry and Pharmacology , Geosciences , Physics
    Notes: A linear least-squares formulation of the method of isomorphous replacement is presented. With data from untwinned crystals, this approach is shown to be equivalent to the phasing representation developed by Hendrickson & Lattman [Acta Cryst. (1970). B26, 136-143]. A general method for calculating the most probable phase is described and applied to the higher- dimensional problem of phase determination for twinned structures. A method for calculating the best phase with intensity data from twinned crystals is also presented. The dependences of these phasing procedures on the number of derivatives and accuracy of the data sets are evaluated in test calculations.
    Type of Medium: Electronic Resource
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  • 6
    Electronic Resource
    Electronic Resource
    [S.l.] : International Union of Crystallography (IUCr)
    Acta crystallographica 45 (1989), S. 309-314 
    ISSN: 1600-5724
    Source: Crystallography Journals Online : IUCR Backfile Archive 1948-2001
    Topics: Chemistry and Pharmacology , Geosciences , Physics
    Notes: In a typical cross-rotation function, the Patterson function of a single search molecule is compared with an observed Patterson function, which contains a set of symmetry-related intramolecular vector sets. In principle, it is better to search for the symmetry- related molecules simultaneously, and Nordman [Am. Crystallogr. Assoc. (1986), Hamilton, Ontario, Program Abstr. p. 36] has reported success with an algorithm of this type. In this paper, the differences between the ordinary search and a simultaneous search are investigated, and it is shown that the combined presence of crystallographic symmetry and approximate symmetry of a search model may lead to significant bias in conventional rotation functions. The nature and magnitude of this symmetry bias are discussed. An efficient algorithm is derived for generating a modified unbiased cross-rotation function map from conventional rotation functions. Two examples are described that demonstrate improvement in the quality of the rotation function maps and the ability to obtain physically meaningful correlation coefficients.
    Type of Medium: Electronic Resource
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  • 7
    Electronic Resource
    Electronic Resource
    [S.l.] : International Union of Crystallography (IUCr)
    Acta crystallographica 44 (1988), S. 142-144 
    ISSN: 1600-5724
    Source: Crystallography Journals Online : IUCR Backfile Archive 1948-2001
    Topics: Chemistry and Pharmacology , Geosciences , Physics
    Notes: The statistics of intensity data from hemihedrally twinned specimens are analyzed in terms of a new parameter and are shown to take a simple form in both the centrosymmetric and non-centrosymmetric cases. This analysis provides a sensitive method for determining the twinning fraction. The effects of intensity measurement errors on the observed statistics are discussed.
    Type of Medium: Electronic Resource
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  • 8
    Electronic Resource
    Electronic Resource
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Biochemistry 58 (1989), S. 607-633 
    ISSN: 0066-4154
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Chemistry and Pharmacology , Biology
    Type of Medium: Electronic Resource
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  • 9
    Electronic Resource
    Electronic Resource
    Copenhagen : International Union of Crystallography (IUCr)
    Applied crystallography online 21 (1988), S. 925-928 
    ISSN: 1600-5767
    Source: Crystallography Journals Online : IUCR Backfile Archive 1948-2001
    Topics: Geosciences , Physics
    Notes: A procedure is described for performing least-squares rigid-body or group refinements in real space. The necessary derivatives are obtained from gradients in a difference Fourier map [Jack & Levitt (1978). Acta Cryst. A34, 931–935] allowing the use of fast Fourier transforms for rapid calculations. The computation time is nearly independent of the number of rigid groups being refined. The orientational transformation of the molecule or group is represented in a linear matrix form. The inherent non-linearity is treated outside of the refinement calculations, and trigonometric calculations are avoided. The linear approximation provides versatility in the types of constraints that may be applied during the refinement. Errors in unit-cell parameters may be detected through the strain component of the transformation matrix. The results of refinement of two protein structures are described as examples.
    Type of Medium: Electronic Resource
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  • 10
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