Better together: building protein oligomers naturally and by design

Protein oligomers are more common in nature than monomers, with dimers being the most prevalent final structural state observed in known structures. From a biological perspective, this makes sense as it conserves vital molecular resources that may be wasted simply by generating larger single polypeptide units, and allows new features such as cooperativity to emerge. Taking inspiration from nature, protein designers and engineers are now building artificial oligomeric complexes using a variety of approaches to generate new and useful supramolecular protein structures. Oligomerisation is thus offering a new approach to sample structure and function space not accessible through simply tinkering with monomeric proteins.

[1]  Osiris Martinez-Guzman,et al.  Heme dynamics and trafficking factors revealed by genetically encoded fluorescent heme sensors , 2016, Proceedings of the National Academy of Sciences.

[2]  M. Scheffner,et al.  Synthesis of defined ubiquitin dimers. , 2010, Journal of the American Chemical Society.

[3]  D. Baker,et al.  Confirmation of intersubunit connectivity and topology of designed protein complexes by native MS , 2018, Proceedings of the National Academy of Sciences.

[4]  K. Oohora,et al.  Hemoprotein-based supramolecular assembling systems. , 2014, Current opinion in chemical biology.

[5]  M. Zheng,et al.  Site-Specific One-to-One Click Coupling of Single Proteins to Individual Carbon Nanotubes: A Single-Molecule Approach. , 2017, Journal of the American Chemical Society.

[6]  L. Regan,et al.  Antiparallel Leucine Zipper-Directed Protein Reassembly: Application to the Green Fluorescent Protein , 2000 .

[7]  Functional modulation and directed assembly of an enzyme through designed non-natural post-translation modification , 2015, Chemical science.

[8]  D. D. Jones,et al.  Controlling self-assembly by linking protein folding, DNA binding, and the redox chemistry of heme. , 2005, Angewandte Chemie.

[9]  R. Jerala,et al.  Towards designing new nano-scale protein architectures. , 2016, Essays in biochemistry.

[10]  Barbara Imperiali,et al.  Protein oligomerization: how and why. , 2005, Bioorganic & medicinal chemistry.

[11]  S. Teichmann,et al.  Principles of assembly reveal a periodic table of protein complexes , 2015, Science.

[12]  Bo Huang,et al.  Covalent Protein Labeling by SpyTag–SpyCatcher in Fixed Cells for Super‐Resolution Microscopy , 2017, Chembiochem : a European journal of chemical biology.

[13]  E. Baker,et al.  Structure of Rhombohedral 2 Zinc Insulin Crystals , 1969, Nature.

[14]  P. Rizkallah,et al.  Genetically encoding phenyl azide chemistry: new uses and ideas for classical biochemistry. , 2013, Biochemical Society transactions.

[15]  A J Olson,et al.  Structural symmetry and protein function. , 2000, Annual review of biophysics and biomolecular structure.

[16]  I. Hamachi,et al.  Recent Progress in Strategies for the Creation of Protein‐Based Fluorescent Biosensors , 2009, Chembiochem : a European journal of chemical biology.

[17]  J. Matthews,et al.  The power of two: protein dimerization in biology. , 2004, Trends in biochemical sciences.

[18]  P G Schultz,et al.  A general method for site-specific incorporation of unnatural amino acids into proteins. , 1989, Science.

[19]  F. Tezcan,et al.  A designed supramolecular protein assembly with in vivo enzymatic activity , 2014, Science.

[20]  R. Tsien,et al.  The Fluorescent Toolbox for Assessing Protein Location and Function , 2006, Science.

[21]  Alexander C Carpenter,et al.  Blueprints for Biosensors: Design, Limitations, and Applications , 2018, Genes.

[22]  T. Yeates,et al.  The design of symmetric protein nanomaterials comes of age in theory and practice. , 2016, Current opinion in structural biology.

[23]  Lu Zhang,et al.  Massively parallel de novo protein design for targeted therapeutics , 2017, Nature.

[24]  Robert E Campbell,et al.  A fluorogenic red fluorescent protein heterodimer. , 2012, Chemistry & biology.

[25]  F. Rutjes,et al.  Strain-Promoted 1,3-Dipolar Cycloaddition of Cycloalkynes and Organic Azides , 2016, Topics in Current Chemistry.

[26]  Ajasja Ljubetič,et al.  Advances in design of protein folds and assemblies. , 2017, Current opinion in chemical biology.

[27]  J. H. Pereira,et al.  Computational Design of Self-Assembling Cyclic Protein Homo-oligomers , 2016, Nature chemistry.

[28]  T. Rich,et al.  Overcoming limitations of FRET measurements , 2016, Cytometry. Part A : the journal of the International Society for Analytical Cytology.

[29]  M. Ubbink,et al.  Dramatic modulation of electron transfer in protein complexes by crosslinking , 2002, Nature Structural Biology.

[30]  Siegfried Labeit,et al.  Titins: Giant Proteins in Charge of Muscle Ultrastructure and Elasticity , 1995, Science.

[31]  Peter G Schultz,et al.  Synthesis of bispecific antibodies using genetically encoded unnatural amino acids. , 2012, Journal of the American Chemical Society.

[32]  Qiu-lin Tang,et al.  Novel Split-Luciferase-Based Genetically Encoded Biosensors for Noninvasive Visualization of Rho GTPases , 2013, PloS one.

[33]  Ingemar André,et al.  Computational design of protein self-assembly. , 2016, Current opinion in structural biology.

[34]  M. Hecht,et al.  Self-Assembling Nano-Architectures Created from a Protein Nano-Building Block Using an Intermolecularly Folded Dimeric de Novo Protein. , 2015, Journal of the American Chemical Society.

[35]  A. Finazzi-Agro’,et al.  The importance of being dimeric , 2004, The FEBS journal.

[36]  P. Rizkallah,et al.  Genetically encoded phenyl azide photochemistry drives positive and negative functional modulation of a red fluorescent protein , 2015 .

[37]  I. M. Klotz Protein subunits: a table. , 1967, Science.

[38]  S. Boxer,et al.  Split Green Fluorescent Proteins: Scope, Limitations, and Outlook. , 2019, Annual review of biophysics.

[39]  Peter G Schultz,et al.  Adding new chemistries to the genetic code. , 2010, Annual review of biochemistry.

[40]  Peter G Schultz,et al.  An Expanded Eukaryotic Genetic Code , 2003, Science.

[41]  A J Olson,et al.  Morphology of protein-protein interfaces. , 1998, Structure.

[42]  M. Hecht,et al.  Self-Assembling Supramolecular Nanostructures Constructed from de Novo Extender Protein Nanobuilding Blocks. , 2018, ACS synthetic biology.

[43]  F. Crick,et al.  Structure of Small Viruses , 1956, Nature.

[44]  Robert E Campbell,et al.  Dimerization-dependent green and yellow fluorescent proteins. , 2012, ACS synthetic biology.

[45]  D. Woolfson,et al.  The de novo design of α-helical peptides for supramolecular self-assembly. , 2019, Current opinion in biotechnology.

[46]  T. Yeates,et al.  Resource A Suite of Engineered GFP Molecules for Oligomeric Scaffolding Graphical Abstract Highlights , 2015 .

[47]  R. Tsien,et al.  green fluorescent protein , 2020, Catalysis from A to Z.

[48]  P. Paoletti,et al.  Genetically encoding a light switch in an ionotropic glutamate receptor reveals subunit-specific interfaces , 2014, Proceedings of the National Academy of Sciences.

[49]  Richard B. Sessions,et al.  Computational design of water-soluble α-helical barrels , 2014, Science.

[50]  R. Tsien,et al.  Fluorescent indicators for Ca2+based on green fluorescent proteins and calmodulin , 1997, Nature.

[51]  Robert E Campbell,et al.  Ratiometric biosensors based on dimerization-dependent fluorescent protein exchange , 2015, Nature Methods.

[52]  Chang‐Deng Hu,et al.  Visualization of interactions among bZIP and Rel family proteins in living cells using bimolecular fluorescence complementation. , 2002, Molecular cell.

[53]  P. Rizkallah,et al.  Positive functional synergy of structurally integrated artificial protein dimers assembled by Click chemistry , 2019, Communications Chemistry.

[54]  S J Remington,et al.  Structural basis for dual excitation and photoisomerization of the Aequorea victoria green fluorescent protein. , 1997, Proceedings of the National Academy of Sciences of the United States of America.

[55]  Johan Hofkens,et al.  Synthesis and single enzyme activity of a clicked lipase-BSA hetero-dimer. , 2006, Chemical communications.

[56]  D. Baker,et al.  High thermodynamic stability of parametrically designed helical bundles , 2014, Science.

[57]  Dong Wook Kim,et al.  Development of a simple method for protein conjugation by copper-free click reaction and its application to antibody-free Western blot analysis. , 2012, Bioconjugate chemistry.

[58]  David Baker,et al.  Accurate design of megadalton-scale two-component icosahedral protein complexes , 2016, Science.

[59]  R. Arai,et al.  Design and construction of self-assembling supramolecular protein complexes using artificial and fusion proteins as nanoscale building blocks. , 2017, Current opinion in biotechnology.

[60]  D. D. Jones,et al.  Functional modulation and directed assembly of an enzyme through designed non-natural post-translation modification , 2015, Chemical science.

[61]  Yuichiro Hori,et al.  [Crystal structure of the Aequorea victoria green fluorescent protein]. , 2007, Tanpakushitsu kakusan koso. Protein, nucleic acid, enzyme.

[62]  D. Baker,et al.  Design of ordered two-dimensional arrays mediated by noncovalent protein-protein interfaces , 2015, Science.

[63]  J. Brodin,et al.  Designed, Helical Protein Nanotubes with Variable Diameters from a Single Building Block. , 2015, Journal of the American Chemical Society.

[64]  P. Rizkallah,et al.  Molecular basis for functional switching of GFP by two disparate non-native post-translational modifications of a phenyl azide reaction handle† †Electronic supplementary information (ESI) available. See DOI: 10.1039/c6sc00944a Click here for additional data file. , 2016, Chemical science.

[65]  J. Changeux,et al.  ON THE NATURE OF ALLOSTERIC TRANSITIONS: A PLAUSIBLE MODEL. , 1965, Journal of molecular biology.

[66]  Robert Huber,et al.  Expansion of the genetic code enables design of a novel "gold" class of green fluorescent proteins. , 2003, Journal of molecular biology.

[67]  Jennifer E. Padilla,et al.  Nanohedra: Using symmetry to design self assembling protein cages, layers, crystals, and filaments , 2001, Proceedings of the National Academy of Sciences of the United States of America.

[68]  C. J. Murray,et al.  Production of site-specific antibody-drug conjugates using optimized non-natural amino acids in a cell-free expression system. , 2014, Bioconjugate chemistry.

[69]  H. Czapinska,et al.  Structural basis for efficient chromophore communication and energy transfer in a constructed didomain protein scaffold. , 2012, Journal of the American Chemical Society.

[70]  P. Rizkallah,et al.  Different photochemical events of a genetically encoded phenyl azide define and modulate GFP fluorescence. , 2013, Angewandte Chemie.

[71]  L. Pauling Protein interactions. Aggregation of globular proteins , 1953 .

[72]  E. Breukink,et al.  Site-specific functionalization of proteins and their applications to therapeutic antibodies , 2014, Computational and structural biotechnology journal.

[73]  B. Zakeri,et al.  Peptide tag forming a rapid covalent bond to a protein, through engineering a bacterial adhesin , 2012, Proceedings of the National Academy of Sciences.

[74]  M. S. Lewis,et al.  Ricin subunit association. Thermodynamics and the role of the disulfide bond in toxicity. , 1986, The Journal of biological chemistry.

[75]  D. Payan,et al.  Detection of programmed cell death using fluorescence energy transfer. , 1998, Nucleic acids research.

[76]  T. Terwilliger,et al.  Engineering and characterization of a superfolder green fluorescent protein , 2006, Nature Biotechnology.

[77]  M. Ohkura,et al.  A high signal-to-noise Ca2+ probe composed of a single green fluorescent protein , 2001, Nature Biotechnology.

[78]  J B Bailey,et al.  Metal-Directed Design of Supramolecular Protein Assemblies. , 2016, Methods in enzymology.

[79]  Igor L. Medintz,et al.  Materials for fluorescence resonance energy transfer analysis: beyond traditional donor-acceptor combinations. , 2006, Angewandte Chemie.

[80]  Carolyn R. Bertozzi,et al.  Copper-free click chemistry for dynamic in vivo imaging , 2007, Proceedings of the National Academy of Sciences.

[81]  Hironori Hayashi,et al.  Design Strategies of Fluorescent Biosensors Based on Biological Macromolecular Receptors , 2010, Sensors.

[82]  Roger Y. Tsien,et al.  Crystal Structure of the Aequorea victoria Green Fluorescent Protein , 1996, Science.

[83]  Kristin N. Parent,et al.  Metal-directed, chemically-tunable assembly of one-, two- and three-dimensional crystalline protein arrays , 2012, Nature chemistry.

[84]  David Baker,et al.  Computational design of a homotrimeric metalloprotein with a trisbipyridyl core , 2016, Proceedings of the National Academy of Sciences.

[85]  Shigeyuki Yokoyama,et al.  Codon reassignment in the Escherichia coli genetic code , 2010, Nucleic acids research.

[86]  D. Bosch,et al.  Construction of a multifunctional enzyme complex via the strain-promoted azide-alkyne cycloaddition. , 2013, Bioconjugate chemistry.

[87]  Stephen L Mayo,et al.  Computational design and experimental verification of a symmetric protein homodimer , 2015, Proceedings of the National Academy of Sciences.