Mechanisms of cellular proteostasis: insights from single molecule approaches (226.3)

Cells employ a variety of strategies to maintain proteome homeostasis. Beginning during protein biogenesis, the translation machinery and a number of molecular chaperones promote correct de novo folding of nascent proteins even before synthesis is complete. Another set of molecular chaperones helps to maintain proteins in their functional, native state. Polypeptides that are no longer needed or pose a threat to the cell, such as misfolded proteins and aggregates, are removed in an efficient and timely fashion by ATP-dependent proteases. In this review, we describe how applications of single-molecule manipulation methods, in particular optical tweezers, are shedding new light on the molecular mechanisms of quality control during the life cycles of proteins.

[1]  Joseph D Puglisi,et al.  Single ribosome dynamics and the mechanism of translation. , 2010, Annual review of biophysics.

[2]  S. Pedersen Escherichia coli ribosomes translate in vivo with variable rate. , 1984, The EMBO journal.

[3]  C. Ratzke,et al.  Heat shock protein 90’s mechanochemical cycle is dominated by thermal fluctuations , 2011, Proceedings of the National Academy of Sciences.

[4]  Andrey Kosolapov,et al.  Tertiary Interactions within the Ribosomal Exit Tunnel , 2009, Nature Structural &Molecular Biology.

[5]  Robert T Sauer,et al.  AAA+ proteases: ATP-fueled machines of protein destruction. , 2011, Annual review of biochemistry.

[6]  C. Jarzynski Nonequilibrium Equality for Free Energy Differences , 1996, cond-mat/9610209.

[7]  Carlos Bustamante,et al.  Optical-trap force transducer that operates by direct measurement of light momentum. , 2003, Methods in enzymology.

[8]  Zoya Ignatova,et al.  Folding at the birth of the nascent chain: coordinating translation with co-translational folding. , 2011, Current opinion in structural biology.

[9]  Andreas Martin,et al.  Distinct static and dynamic interactions control ATPase-peptidase communication in a AAA+ protease. , 2007, Molecular cell.

[10]  Daniel N. Wilson,et al.  The ribosomal tunnel as a functional environment for nascent polypeptide folding and translational stalling. , 2011, Current opinion in structural biology.

[11]  R. Perez-Jimenez,et al.  Mechanical Unfolding Pathways of the Enhanced Yellow Fluorescent Protein Revealed by Single Molecule Force Spectroscopy* , 2006, Journal of Biological Chemistry.

[12]  T. Springer,et al.  Calcium stabilizes the von Willebrand factor A2 domain by promoting refolding , 2012, Proceedings of the National Academy of Sciences.

[13]  Daniel N. Wilson,et al.  Structural basis for translational stalling by human cytomegalovirus and fungal arginine attenuator peptide. , 2010, Molecular cell.

[14]  Carlos Bustamante,et al.  Recent advances in optical tweezers. , 2008, Annual review of biochemistry.

[15]  S. Tans,et al.  Direct Observation of Chaperone-Induced Changes in a Protein Folding Pathway , 2007, Science.

[16]  W. Skach,et al.  Ligand-driven vectorial folding of ribosome-bound human CFTR NBD1. , 2011, Molecular cell.

[17]  I. Tinoco,et al.  The Ribosome Modulates Nascent Protein Folding , 2011, Science.

[18]  Carlos Bustamante,et al.  Differential detection of dual traps improves the spatial resolution of optical tweezers. , 2006, Proceedings of the National Academy of Sciences of the United States of America.

[19]  Robert T Sauer,et al.  Partitioning between unfolding and release of native domains during ClpXP degradation determines substrate selectivity and partial processing. , 2005, Proceedings of the National Academy of Sciences of the United States of America.

[20]  H. Gaub,et al.  Unfolding pathways of individual bacteriorhodopsins. , 2000, Science.

[21]  A. Horwich,et al.  Chaperone rings in protein folding and degradation. , 1999, Proceedings of the National Academy of Sciences of the United States of America.

[22]  J. Hoskins,et al.  The Interplay of ClpXP with the Cell Division Machinery in Escherichia coli , 2011, Journal of bacteriology.

[23]  A. Ashkin Acceleration and trapping of particles by radiation pressure , 1970 .

[24]  Philip Coffino,et al.  Glycine–alanine repeats impair proper substrate unfolding by the proteasome , 2006, The EMBO journal.

[25]  Lisa D. Cabrita,et al.  Structure, dynamics and folding of an immunoglobulin domain of the gelation factor (ABP-120) from Dictyostelium discoideum. , 2009, Journal of molecular biology.

[26]  John D Chodera,et al.  The molten globule state is unusually deformable under mechanical force , 2012, Proceedings of the National Academy of Sciences.

[27]  Philip Coffino,et al.  Slippery Substrates Impair Function of a Bacterial Protease ATPase by Unbalancing Translocation versus Exit* , 2013, The Journal of Biological Chemistry.

[28]  Nancy R Forde,et al.  Mechanical processes in biochemistry. , 2004, Annual review of biochemistry.

[29]  Everett A Lipman,et al.  Single-molecule spectroscopy of protein folding in a chaperonin cage , 2010, Proceedings of the National Academy of Sciences.

[30]  J. Frydman,et al.  The ribosome as a hub for protein quality control. , 2013, Molecular cell.

[31]  Andrew R. Nager,et al.  Dynamic and static components power unfolding in topologically closed rings of a AAA+ proteolytic machine , 2012, Nature Structural &Molecular Biology.

[32]  Marco Gartmann,et al.  α-Helical nascent polypeptide chains visualized within distinct regions of the ribosomal exit tunnel , 2010, Nature Structural &Molecular Biology.

[33]  H. Bernstein,et al.  Translation arrest requires two-way communication between a nascent polypeptide and the ribosome. , 2006, Molecular cell.

[34]  G. I. Bell Models for the specific adhesion of cells to cells. , 1978, Science.

[35]  L. Goldstein,et al.  Biophysical challenges to axonal transport: motor-cargo deficiencies and neurodegeneration. , 2014, Annual review of biophysics.

[36]  G. Marczynski,et al.  Regulated degradation of chromosome replication proteins DnaA and CtrA in Caulobacter crescentus , 2004, Molecular microbiology.

[37]  F. Hartl,et al.  Chaperonin-Catalyzed Rescue of Kinetically Trapped States in Protein Folding , 2010, Cell.

[38]  Samrat Mukhopadhyay,et al.  Single-molecule biophysics: at the interface of biology, physics and chemistry , 2008, Journal of The Royal Society Interface.

[39]  J. Hoskins,et al.  Binding and Degradation of Heterodimeric Substrates by ClpAP and ClpXP* , 2005, Journal of Biological Chemistry.

[40]  S. Lindquist,et al.  Optical trapping with high forces reveals unexpected behaviors of prion fibrils , 2010, Nature Structural &Molecular Biology.

[41]  Elizabeth A. Shank,et al.  The folding cooperativity of a protein is controlled by its chain topology , 2010, Nature.

[42]  Alessandro Borgia,et al.  Single-molecule studies of protein folding. , 2008, Annual review of biochemistry.

[43]  R. Hegde,et al.  Design principles of protein biosynthesis-coupled quality control. , 2012, Developmental cell.

[44]  D. Thirumalai,et al.  From mechanical folding trajectories to intrinsic energy landscapes of biopolymers , 2013, Proceedings of the National Academy of Sciences.

[45]  C. Tu,et al.  Pentobarbital-induced Changes in Drosophila Glutathione S-Transferase D21 mRNA Stability (*) , 1995, The Journal of Biological Chemistry.

[46]  Robert T Sauer,et al.  Protein unfolding by a AAA+ protease is dependent on ATP-hydrolysis rates and substrate energy landscapes , 2008, Nature Structural &Molecular Biology.

[47]  M. Maurizi,et al.  Crystal structure at 1.9A of E. coli ClpP with a peptide covalently bound at the active site. , 2006, Journal of structural biology.

[48]  Toshio Ando,et al.  Video imaging of walking myosin V by high-speed atomic force microscopy , 2010, Nature.

[49]  Carlos Bustamante,et al.  Grabbing the cat by the tail: manipulating molecules one by one , 2000, Nature Reviews Molecular Cell Biology.

[50]  Hong Qian,et al.  Statistics and Related Topics in Single-Molecule Biophysics. , 2014, Annual review of statistics and its application.

[51]  G. Hummer,et al.  Theory, analysis, and interpretation of single-molecule force spectroscopy experiments , 2008, Proceedings of the National Academy of Sciences.

[52]  Adrian O. Olivares,et al.  Single-Molecule Protein Unfolding and Translocation by an ATP-Fueled Proteolytic Machine , 2011, Cell.

[53]  T. Baker,et al.  Unique contacts direct high-priority recognition of the tetrameric Mu transposase-DNA complex by the AAA+ unfoldase ClpX. , 2008, Molecular cell.

[54]  F. Hartl,et al.  Real-time observation of trigger factor function on translating ribosomes , 2006, Nature.

[55]  Jianli Lu,et al.  Folding zones inside the ribosomal exit tunnel , 2005, Nature Structural &Molecular Biology.

[56]  S. Glynn,et al.  Structures of Asymmetric ClpX Hexamers Reveal Nucleotide-Dependent Motions in a AAA+ Protein-Unfolding Machine , 2009, Cell.

[57]  S. Cavagnero,et al.  Chain dynamics of nascent polypeptides emerging from the ribosome. , 2008, ACS chemical biology.

[58]  S. Chu,et al.  Observation of a single-beam gradient force optical trap for dielectric particles. , 1986, Optics letters.

[59]  K A Dill,et al.  Stabilization of proteins in confined spaces. , 2001, Biochemistry.

[60]  I. Tinoco,et al.  Equilibrium Information from Nonequilibrium Measurements in an Experimental Test of Jarzynski's Equality , 2002, Science.

[61]  E. Siggia,et al.  Entropic elasticity of lambda-phage DNA. , 1994, Science.

[62]  Tania A. Baker,et al.  Pore loops of the AAA+ ClpX machine grip substrates to drive translocation and unfolding , 2008, Nature Structural &Molecular Biology.

[63]  Hani S. Zaher,et al.  Fidelity at the Molecular Level: Lessons from Protein Synthesis , 2009, Cell.

[64]  Shashi Bhushan,et al.  SecM-Stalled Ribosomes Adopt an Altered Geometry at the Peptidyl Transferase Center , 2011, PLoS biology.

[65]  Hiroyasu Itoh,et al.  Coupling of Rotation and Catalysis in F1-ATPase Revealed by Single-Molecule Imaging and Manipulation , 2007, Cell.

[66]  Carlos Bustamante,et al.  Direct Observation of the Three-State Folding of a Single Protein Molecule , 2005, Science.

[67]  Piotr E. Marszalek,et al.  Stretching single molecules into novel conformations using the atomic force microscope , 2000, Nature Structural Biology.

[68]  Daniel N. Wilson,et al.  Probing translation with small-molecule inhibitors. , 2010, Chemistry & biology.

[69]  Tania A. Baker,et al.  Linkage between ATP Consumption and Mechanical Unfolding during the Protein Processing Reactions of an AAA+ Degradation Machine , 2003, Cell.

[70]  W E Moerner,et al.  Sensing cooperativity in ATP hydrolysis for single multisubunit enzymes in solution , 2011, Proceedings of the National Academy of Sciences.

[71]  C. Jarzynski,et al.  Verification of the Crooks fluctuation theorem and recovery of RNA folding free energies , 2005, Nature.

[72]  Tania A. Baker,et al.  Rebuilt AAA + motors reveal operating principles for ATP-fuelled machines , 2005, Nature.

[73]  G. Crooks Entropy production fluctuation theorem and the nonequilibrium work relation for free energy differences. , 1999, Physical review. E, Statistical physics, plasmas, fluids, and related interdisciplinary topics.

[74]  H. Walden,et al.  The Fanconi anemia DNA repair pathway: structural and functional insights into a complex disorder. , 2014, Annual review of biophysics.

[75]  T. Ha,et al.  Ultrahigh-resolution optical trap with single-fluorophore sensitivity , 2011, Nature Methods.

[76]  R. Sauer,et al.  The ClpXP and ClpAP proteases degrade proteins with carboxy-terminal peptide tails added by the SsrA-tagging system. , 1998, Genes & development.

[77]  H. Kramers Brownian motion in a field of force and the diffusion model of chemical reactions , 1940 .

[78]  D. F. Smith,et al.  Dynamics of heat shock protein 90-progesterone receptor binding and the disactivation loop model for steroid receptor complexes. , 1993, Molecular endocrinology.

[79]  Shang-Te Danny Hsu,et al.  Structure and dynamics of a ribosome-bound nascent chain by NMR spectroscopy , 2007, Proceedings of the National Academy of Sciences.

[80]  Gene-Wei Li,et al.  Central dogma at the single-molecule level in living cells , 2011, Nature.

[81]  Joachim Frank,et al.  Structure and dynamics of a processive Brownian motor: the translating ribosome. , 2010, Annual review of biochemistry.

[82]  J. Buchner,et al.  Dynamics of heat shock protein 90 C-terminal dimerization is an important part of its conformational cycle , 2010, Proceedings of the National Academy of Sciences.

[83]  Changbong Hyeon,et al.  Revealing the bifurcation in the unfolding pathways of GFP by using single-molecule experiments and simulations , 2007, Proceedings of the National Academy of Sciences.

[84]  R. Moritz,et al.  C-terminal Extension of Truncated Recombinant Proteins in Escherichia coli with a 10Sa RNA Decapeptide(*) , 1995, The Journal of Biological Chemistry.

[85]  Carlos Bustamante,et al.  In singulo biochemistry: when less is more. , 2008, Annual review of biochemistry.

[86]  Jens Michaelis,et al.  Mechanism of Force Generation of a Viral DNA Packaging Motor , 2005, Cell.

[87]  Carlos Bustamante,et al.  ClpX(P) Generates Mechanical Force to Unfold and Translocate Its Protein Substrates , 2011, Cell.

[88]  Ignacio Tinoco,et al.  Following translation by single ribosomes one codon at a time , 2008, Nature.

[89]  M. Rief,et al.  The Complex Folding Network of Single Calmodulin Molecules , 2011, Science.

[90]  Andreas Matouschek,et al.  Finding a protein's Achilles heel , 2003, Nature Structural Biology.

[91]  Andreas Bracher,et al.  Molecular chaperones in protein folding and proteostasis , 2011, Nature.

[92]  Peter G Wolynes,et al.  Electrostatic effects on funneled landscapes and structural diversity in denatured protein ensembles , 2009, Proceedings of the National Academy of Sciences.

[93]  Bernd Bukau,et al.  The ribosome as a platform for co-translational processing, folding and targeting of newly synthesized proteins , 2009, Nature Structural &Molecular Biology.

[94]  Martin Hessling,et al.  The large conformational changes of Hsp90 are only weakly coupled to ATP hydrolysis , 2009, Nature Structural &Molecular Biology.

[95]  Michele Vendruscolo,et al.  New scenarios of protein folding can occur on the ribosome. , 2011, Journal of the American Chemical Society.

[96]  Yodai Takei,et al.  Single-molecule Observation of Protein Folding in Symmetric GroEL-(GroES)2 Complexes* , 2012, The Journal of Biological Chemistry.

[97]  Greg L. Hersch,et al.  Sculpting the Proteome with AAA+ Proteases and Disassembly Machines , 2004, Cell.

[98]  J. Frydman,et al.  Action of the chaperonin GroEL/ES on a non-native substrate observed with single-molecule FRET. , 2010, Journal of molecular biology.

[99]  T. Baker,et al.  Role of the processing pore of the ClpX AAA+ ATPase in the recognition and engagement of specific protein substrates. , 2004, Genes & development.

[100]  J. Puglisi,et al.  Single-molecule analysis of translational dynamics. , 2012, Cold Spring Harbor perspectives in biology.

[101]  I. Tinoco,et al.  Biological mechanisms, one molecule at a time. , 2011, Genes & development.

[102]  S. Tans,et al.  Reshaping of the conformational search of a protein by the chaperone trigger factor , 2013, Nature.