NMR reveals novel mechanisms of protein activity regulation

NMR spectroscopy is one of the most powerful tools for the characterization of biomolecular systems. A unique aspect of NMR is its capacity to provide an integrated insight into both the structure and intrinsic dynamics of biomolecules. In addition, NMR can provide site‐resolved information about the conformation entropy of binding, as well as about energetically excited conformational states. Recent advances have enabled the application of NMR for the characterization of supramolecular systems. A summary of mechanisms underpinning protein activity regulation revealed by the application of NMR spectroscopy in a number of biological systems studied in the lab is provided.

[1]  Charalampos G. Kalodimos,et al.  Protein dynamics and allostery: an NMR view. , 2011, Current opinion in structural biology.

[2]  J Patrick Loria,et al.  Nanometer propagation of millisecond motions in V-type allostery. , 2010, Structure.

[3]  Paramita Sarkar,et al.  Structural basis for regulation of the Crk signaling protein by a proline switch , 2010, Nature chemical biology.

[4]  Andrew L. Lee,et al.  Using NMR to study fast dynamics in proteins: methods and applications. , 2010, Current opinion in pharmacology.

[5]  R. Nussinov,et al.  Allostery and population shift in drug discovery. , 2010, Current opinion in pharmacology.

[6]  Tao Yu,et al.  Dynamics connect substrate recognition to catalysis in protein kinase A. , 2010, Nature chemical biology.

[7]  Dmitry M Korzhnev,et al.  A Transient and Low-Populated Protein-Folding Intermediate at Atomic Resolution , 2010, Science.

[8]  S. Freund,et al.  NMR resonance assignments of thrombin reveal the conformational and dynamic effects of ligation , 2010, Proceedings of the National Academy of Sciences.

[9]  Thomas A. Milne,et al.  Pro Isomerization in MLL1 PHD3-Bromo Cassette Connects H3K4me Readout to CyP33 and HDAC-Mediated Repression , 2010, Cell.

[10]  A. Joshua Wand,et al.  The role of conformational entropy in molecular recognition by calmodulin , 2010, Nature chemical biology.

[11]  L. Kay,et al.  Dynamic Regulation of Archaeal Proteasome Gate Opening As Studied by TROSY NMR , 2010, Science.

[12]  Jodi Gureasko,et al.  Role of the histone domain in the autoinhibition and activation of the Ras activator Son of Sevenless , 2010, Proceedings of the National Academy of Sciences.

[13]  D. Cowburn,et al.  A Conformational Switch in the Scaffolding Protein NHERF1 Controls Autoinhibition and Complex Formation* , 2009, The Journal of Biological Chemistry.

[14]  D. Beckett.  Regulating transcription regulators via allostery and flexibility , 2009, Proceedings of the National Academy of Sciences.

[15]  L. Kay,et al.  Observing biological dynamics at atomic resolution using NMR. , 2009, Trends in biochemical sciences.

[16]  Charalampos G. Kalodimos,et al.  Dynamic activation of an allosteric regulatory protein , 2009, Nature.

[17]  L. Kay,et al.  NMR spectroscopy brings invisible protein states into focus. , 2009, Nature chemical biology.

[18]  R. Nussinov,et al.  The role of dynamic conformational ensembles in biomolecular recognition. , 2009, Nature chemical biology.

[19]  Andrew L. Lee,et al.  Hidden dynamic allostery in a PDZ domain , 2009, Proceedings of the National Academy of Sciences.

[20]  V. Hilser,et al.  Rational modulation of conformational fluctuations in adenylate kinase reveals a local unfolding mechanism for allostery and functional adaptation in proteins , 2009, Proceedings of the National Academy of Sciences.

[21]  M. Lemmon,et al.  ErbB2 resembles an autoinhibited invertebrate epidermal growth factor receptor , 2009, Nature.

[22]  H. Won,et al.  Structural overview on the allosteric activation of cyclic AMP receptor protein. , 2009, Biochimica et biophysica acta.

[23]  R. Birge,et al.  Crk and CrkL adaptor proteins: networks for physiological and pathological signaling , 2009, Cell Communication and Signaling.

[24]  Rajeevan Selvaratnam,et al.  Dynamically Driven Ligand Selectivity in Cyclic Nucleotide Binding Domains* , 2009, The Journal of Biological Chemistry.

[25]  R. Ebright,et al.  Structural basis for cAMP-mediated allosteric control of the catabolite activator protein , 2009, Proceedings of the National Academy of Sciences.

[26]  Lila M. Gierasch,et al.  Sending Signals Dynamically , 2009, Science.

[27]  R. Joseph,et al.  Proline isomerization preorganizes the Itk SH2 domain for binding to the Itk SH3 domain. , 2009, Journal of molecular biology.

[28]  Andrew L. Lee,et al.  Dynamic dysfunction in dihydrofolate reductase results from antifolate drug binding: modulation of dynamics within a structural state. , 2009, Structure.

[29]  Paul Schanda,et al.  Direct observation of the dynamic process underlying allosteric signal transmission. , 2009, Journal of the American Chemical Society.

[30]  Aron W Fenton,et al.  Allostery: an illustrated definition for the 'second secret of life'. , 2008, Trends in biochemical sciences.

[31]  Jimin Wang,et al.  A regulatable switch mediates self-association in an immunoglobulin fold , 2008, Nature Structural &Molecular Biology.

[32]  N. Goodey,et al.  Allosteric regulation and catalysis emerge via a common route. , 2008, Nature chemical biology.

[33]  Rajeevan Selvaratnam,et al.  Entropy-driven cAMP-dependent Allosteric Control of Inhibitory Interactions in Exchange Proteins Directly Activated by cAMP* , 2008, Journal of Biological Chemistry.

[34]  K. Gardner,et al.  Estimation of the available free energy in a LOV2-J alpha photoswitch. , 2008, Nature chemical biology.

[35]  Oliver F. Lange,et al.  Recognition Dynamics Up to Microseconds Revealed from an RDC-Derived Ubiquitin Ensemble in Solution , 2008, Science.

[36]  S. Pochapsky,et al.  A functional proline switch in cytochrome P450cam. , 2008, Structure.

[37]  G. Amarasinghe,et al.  Internal dynamics control activation and activity of the autoinhibited Vav DH domain , 2008, Nature Structural &Molecular Biology.

[38]  R. Nussinov,et al.  Allostery: absence of a change in shape does not imply that allostery is not at play. , 2008, Journal of molecular biology.

[39]  M. Buck,et al.  Compensatory and long-range changes in picosecond-nanosecond main-chain dynamics upon complex formation: 15N relaxation analysis of the free and bound states of the ubiquitin-like domain of human plexin-B1 and the small GTPase Rac1. , 2008, Journal of molecular biology.

[40]  Nathaniel J. Traaseth,et al.  Allosteric cooperativity in protein kinase A , 2008, Proceedings of the National Academy of Sciences.

[41]  John Kuriyan,et al.  The origin of protein interactions and allostery in colocalization , 2007, Nature.

[42]  D. Kern,et al.  Dynamic personalities of proteins , 2007, Nature.

[43]  Susan S. Taylor,et al.  Evolution of allostery in the cyclic nucleotide binding module , 2007, Genome Biology.

[44]  Pramodh Vallurupalli,et al.  Measurement of bond vector orientations in invisible excited states of proteins , 2007, Proceedings of the National Academy of Sciences.

[45]  S. Karamanou,et al.  Structural Basis for Signal-Sequence Recognition by the Translocase Motor SecA as Determined by NMR , 2007, Cell.

[46]  S. Karamanou,et al.  Bacterial protein secretion through the translocase nanomachine , 2007, Nature Reviews Microbiology.

[47]  G. Clore,et al.  Open-to-closed transition in apo maltose-binding protein observed by paramagnetic NMR , 2007, Nature.

[48]  A. Palmer,et al.  Characterization of chemical exchange using residual dipolar coupling. , 2007, Journal of the American Chemical Society.

[49]  L. Nicholson,et al.  Prolyl cis-trans isomerization as a molecular timer. , 2007, Nature chemical biology.

[50]  L. Kay,et al.  Solution NMR of supramolecular complexes: providing new insights into function , 2007, Nature Methods.

[51]  A. Wand,et al.  Conformational entropy in molecular recognition by proteins , 2007, Nature.

[52]  Michele Vendruscolo,et al.  Protein structure determination from NMR chemical shifts , 2007, Proceedings of the National Academy of Sciences.

[53]  L. Kay,et al.  A solution NMR study showing that active site ligands and nucleotides directly perturb the allosteric equilibrium in aspartate transcarbamoylase , 2007, Proceedings of the National Academy of Sciences.

[54]  V. Hilser,et al.  Intrinsic disorder as a mechanism to optimize allosteric coupling in proteins , 2007, Proceedings of the National Academy of Sciences.

[55]  Dmitry M Korzhnev,et al.  Propagation of dynamic changes in barnase upon binding of barstar: an NMR and computational study. , 2007, Journal of molecular biology.

[56]  L. Nicholson,et al.  The prolyl isomerase Pin1 regulates amyloid precursor protein processing and amyloid-β production , 2007, Nature.

[57]  S. Cusack,et al.  Structure of dimeric SecA, the Escherichia coli preprotein translocase motor. , 2007, Journal of molecular biology.

[58]  L. Nicholson,et al.  Prolyl cis-trans Isomerization as a molecular timer in Crk signaling. , 2007, Molecular cell.

[59]  R. Birge,et al.  Proline cis-trans isomerization controls autoinhibition of a signaling protein. , 2007, Molecular cell.

[60]  Lewis E. Kay,et al.  Quantitative dynamics and binding studies of the 20S proteasome by NMR , 2007, Nature.

[61]  D. Boehr,et al.  The Dynamic Energy Landscape of Dihydrofolate Reductase Catalysis , 2006, Science.

[62]  Christopher J. Nelson,et al.  Proline Isomerization of Histone H3 Regulates Lysine Methylation and Gene Expression , 2006, Cell.

[63]  R. Ebright,et al.  Dynamically driven protein allostery , 2006, Nature Structural &Molecular Biology.

[64]  J. Lindsley,et al.  Whence cometh the allosterome? , 2006, Proceedings of the National Academy of Sciences of the United States of America.

[65]  Dimitra Keramisanou,et al.  Disorder-order folding transitions underlie catalysis in the helicase motor of SecA , 2006, Nature Structural &Molecular Biology.

[66]  Andrew L. Lee,et al.  Dynamic coupling and allosteric behavior in a nonallosteric protein. , 2006, Biochemistry.

[67]  Lewis E. Kay,et al.  New Tools Provide New Insights in NMR Studies of Protein Dynamics , 2006, Science.

[68]  L. Nicholson,et al.  The prolyl isomerase Pin1 regulates amyloid precursor protein processing and amyloid-β production , 2006, Nature.

[69]  Bernd Bukau,et al.  Allosteric regulation of Hsp70 chaperones by a proline switch. , 2006, Molecular cell.

[70]  Walid A Houry,et al.  Quantitative NMR spectroscopy of supramolecular complexes: dynamic side pores in ClpP are important for product release. , 2005, Proceedings of the National Academy of Sciences of the United States of America.

[71]  Henry A. Lester,et al.  Cis–trans isomerization at a proline opens the pore of a neurotransmitter-gated ion channel , 2005, Nature.

[72]  L. Kay,et al.  Intrinsic dynamics of an enzyme underlies catalysis , 2005, Nature.

[73]  L. Kay,et al.  Methyl Groups as Probes of Structure and Dynamics in NMR Studies of High‐Molecular‐Weight Proteins , 2005, Chembiochem : a European journal of chemical biology.

[74]  Andreas Martin,et al.  Prolyl isomerization as a molecular timer in phage infection , 2005, Nature Structural &Molecular Biology.

[75]  J. Changeux,et al.  Allosteric Mechanisms of Signal Transduction , 2005, Science.

[76]  K. Lu,et al.  Phosphorylation-specific prolyl isomerization: is there an underlying theme? , 2005, Nature Cell Biology.

[77]  Susan S. Taylor,et al.  The cAMP binding domain: an ancient signaling module. , 2005, Proceedings of the National Academy of Sciences of the United States of America.

[78]  T. Rapoport,et al.  A large conformational change of the translocation ATPase SecA. , 2004, Proceedings of the National Academy of Sciences of the United States of America.

[79]  A. Palmer,et al.  NMR characterization of the dynamics of biomacromolecules. , 2004, Chemical reviews.

[80]  L. Kay,et al.  An Isotope Labeling Strategy for Methyl TROSY Spectroscopy , 2004, Journal of biomolecular NMR.

[81]  D. Kern,et al.  The role of dynamics in allosteric regulation. , 2003, Current opinion in structural biology.

[82]  Heidi J Sofia,et al.  Phylogeny of the bacterial superfamily of Crp-Fnr transcription regulators: exploiting the metabolic spectrum by controlling alternative gene programs. , 2003, FEMS microbiology reviews.

[83]  L. Kay,et al.  Cross-correlated relaxation enhanced 1H[bond]13C NMR spectroscopy of methyl groups in very high molecular weight proteins and protein complexes. , 2003, Journal of the American Chemical Society.

[84]  A. Andreotti,et al.  Native state proline isomerization: an intrinsic molecular switch. , 2003, Biochemistry.

[85]  J. Deisenhofer,et al.  Nucleotide Control of Interdomain Interactions in the Conformational Reaction Cycle of SecA , 2002, Science.

[86]  J. Kuriyan,et al.  The Conformational Plasticity of Protein Kinases , 2002, Cell.

[87]  A. Andreotti,et al.  Regulation of the tyrosine kinase Itk by the peptidyl-prolyl isomerase cyclophilin A , 2002, Proceedings of the National Academy of Sciences of the United States of America.

[88]  A. Joshua Wand,et al.  Dynamic activation of protein function: A view emerging from NMR spectroscopy , 2001, Nature Structural Biology.

[89]  Frederick W. Dahlquist,et al.  Studying excited states of proteins by NMR spectroscopy , 2001, Nature Structural Biology.

[90]  T. Hunter,et al.  Oncogenic kinase signalling , 2001, Nature.

[91]  D E Wemmer,et al.  Two-state allosteric behavior in a single-domain signaling protein. , 2001, Science.

[92]  T. Steitz,et al.  Modeling the cAMP-induced allosteric transition using the crystal structure of CAP-cAMP at 2.1 A resolution. , 2000, Journal of molecular biology.

[93]  Xin-Yun Huang,et al.  Structural Basis for Relief of Autoinhibition of the Dbl Homology Domain of Proto-Oncogene Vav by Tyrosine Phosphorylation , 2000, Cell.

[94]  B. Kemp,et al.  Active site-directed protein regulation , 1999, Nature.

[95]  A. Palmer,et al.  Temperature dependence of intramolecular dynamics of the basic leucine zipper of GCN4: implications for the entropy of association with DNA. , 1999, Journal of molecular biology.

[96]  M. Page,et al.  Structure and function of the dihydropteroate synthase from Staphylococcus aureus. , 1997, Journal of molecular biology.

[97]  D. Koshland.  The structural basis of negative cooperativity: receptors and enzymes. , 1996, Current opinion in structural biology.

[98]  A J Wand,et al.  Insights into the local residual entropy of proteins provided by NMR relaxation , 1996, Protein science : a publication of the Protein Society.

[99]  L. Kay,et al.  Contributions to conformational entropy arising from bond vector fluctuations measured from NMR-derived order parameters: application to protein folding. , 1996, Journal of molecular biology.

[100]  J. Luban,et al.  Specific incorporation of cyclophilin A into HIV-1 virions , 1994, Nature.

[101]  A. Leslie,et al.  Structural evidence for ligand-induced sequential conformational changes in glyceraldehyde 3-phosphate dehydrogenase. , 1984, Journal of molecular biology.

[102]  L. Nicholson,et al.  Structural biology: The twist in Crk signaling revealed. , 2011, Nature chemical biology.

[103]  A. Wittinghofer,et al.  Capturing cyclic nucleotides in action: snapshots from crystallographic studies , 2007, Nature Reviews Molecular Cell Biology.

[104]  M. Pufall,et al.  Autoinhibitory domains: modular effectors of cellular regulation. , 2002, Annual review of cell and developmental biology.