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Atomic view of the energy landscape in the allosteric regulation of Abl kinase.

Saleh T, Rossi P, Kalodimos CG
Nat Struct Mol Biol 24 893-901 (2017)
Cited: 35 times
EuropePMC logo PMID: 28945248

Abstract

The activity of protein kinases is often regulated in an intramolecular fashion by signaling domains, which feature several phosphorylation or protein-docking sites. How kinases integrate such distinct binding and signaling events to regulate their activities is unclear, especially in quantitative terms. We used NMR spectroscopy to show how structural elements within the Abl regulatory module (RM) synergistically generate a multilayered allosteric mechanism that enables Abl kinase to function as a finely tuned switch. We dissected the structure and energetics of the regulatory mechanism to precisely measure the effects of various activating or inhibiting stimuli on Abl kinase activity. The data provide a mechanistic basis explaining genetic observations and reveal a previously unknown activator region within Abl. Our findings show that drug-resistance mutations in the Abl RM exert their allosteric effect by promoting the activated state of Abl and not by decreasing the drug affinity for the kinase.

Reviews - 6amv mentioned but not cited (1)

  1. Dynamic regulatory features of the protein tyrosine kinases. Amatya N, Lin DY, Andreotti AH. Biochem Soc Trans 47 1101-1116 (2019)

Articles - 6amv mentioned but not cited (1)

  1. Atomic view of the energy landscape in the allosteric regulation of Abl kinase. Saleh T, Rossi P, Kalodimos CG. Nat Struct Mol Biol 24 893-901 (2017)


Reviews citing this publication (12)

  1. The Src module: an ancient scaffold in the evolution of cytoplasmic tyrosine kinases. Shah NH, Amacher JF, Nocka LM, Kuriyan J. Crit Rev Biochem Mol Biol 53 535-563 (2018)
  2. Generic nature of the condensed states of proteins. Fuxreiter M, Vendruscolo M. Nat Cell Biol 23 587-594 (2021)
  3. Intramolecular Fuzzy Interactions Involving Intrinsically Disordered Domains. Arbesú M, Iruela G, Fuentes H, Teixeira JMC, Pons M. Front Mol Biosci 5 39 (2018)
  4. Chemical shift-based methods in NMR structure determination. Nerli S, McShan AC, Sgourakis NG. Prog Nucl Magn Reson Spectrosc 106-107 1-25 (2018)
  5. Allosteric Regulation at the Crossroads of New Technologies: Multiscale Modeling, Networks, and Machine Learning. Verkhivker GM, Agajanian S, Hu G, Tao P. Front Mol Biosci 7 136 (2020)
  6. Allostery: Allosteric Cancer Drivers and Innovative Allosteric Drugs. Nussinov R, Zhang M, Maloney R, Liu Y, Tsai CJ, Jang H. J Mol Biol 434 167569 (2022)
  7. Spotlight on the Ballet of Proteins: The Structural Dynamic Properties of Proteins Illuminated by Solution NMR. Tokunaga Y, Viennet T, Arthanari H, Takeuchi K. Int J Mol Sci 21 E1829 (2020)
  8. Reining in BTK: Interdomain Interactions and Their Importance in the Regulatory Control of BTK. Kueffer LE, Joseph RE, Andreotti AH. Front Cell Dev Biol 9 655489 (2021)
  9. Allosteric regulation and inhibition of protein kinases. Mingione VR, Paung Y, Outhwaite IR, Seeliger MA. Biochem Soc Trans 51 373-385 (2023)
  10. Dynamic equilibria in protein kinases. Pegram LM, Anderson JW, Ahn NG. Curr Opin Struct Biol 71 215-222 (2021)
  11. Protein conformational ensembles in function: roles and mechanisms. Nussinov R, Liu Y, Zhang W, Jang H. RSC Chem Biol 4 850-864 (2023)
  12. The "violin model": Looking at community networks for dynamic allostery. Madan LK, Welsh CL, Kornev AP, Taylor SS. J Chem Phys 158 081001 (2023)

Articles citing this publication (21)

  1. Conformational states dynamically populated by a kinase determine its function. Xie T, Saleh T, Rossi P, Kalodimos CG. Science 370 eabc2754 (2020)
  2. Sphingosine-1-Phosphate Receptor 1 Activity Promotes Tumor Growth by Amplifying VEGF-VEGFR2 Angiogenic Signaling. Balaji Ragunathrao VA, Anwar M, Akhter MZ, Chavez A, Mao Y, Natarajan V, Lakshmikanthan S, Chrzanowska-Wodnicka M, Dudek AZ, Claesson-Welsh L, Kitajewski JK, Wary KK, Malik AB, Mehta D. Cell Rep 29 3472-3487.e4 (2019)
  3. Enrichment of Aurora B kinase at the inner kinetochore controls outer kinetochore assembly. Bonner MK, Haase J, Swinderman J, Halas H, Miller Jenkins LM, Kelly AE. J Cell Biol 218 3237-3257 (2019)
  4. A distal regulatory region of a class I human histone deacetylase. Werbeck ND, Shukla VK, Kunze MBA, Yalinca H, Pritchard RB, Siemons L, Mondal S, Greenwood SOR, Kirkpatrick J, Marson CM, Hansen DF. Nat Commun 11 3841 (2020)
  5. Cumulative mechanism of several major imatinib-resistant mutations in Abl kinase. Hoemberger M, Pitsawong W, Kern D. Proc Natl Acad Sci U S A 117 19221-19227 (2020)
  6. Allosteric pluripotency as revealed by protein kinase A. Byun JA, Akimoto M, VanSchouwen B, Lazarou TS, Taylor SS, Melacini G. Sci Adv 6 eabb1250 (2020)
  7. Mutation in Abl kinase with altered drug-binding kinetics indicates a novel mechanism of imatinib resistance. Lyczek A, Berger BT, Rangwala AM, Paung Y, Tom J, Philipose H, Guo J, Albanese SK, Robers MB, Knapp S, Chodera JD, Seeliger MA. Proc Natl Acad Sci U S A 118 e2111451118 (2021)
  8. Conformational equilibrium defines the variable induction of the multidrug-binding transcriptional repressor QacR. Takeuchi K, Imai M, Shimada I. Proc Natl Acad Sci U S A 116 19963-19972 (2019)
  9. A Conserved Allosteric Pathway in Tyrosine Kinase Regulation. Marsiglia WM, Katigbak J, Zheng S, Mohammadi M, Zhang Y, Traaseth NJ. Structure 27 1308-1315.e3 (2019)
  10. Structural Basis for the Inhibition of the Autophosphorylation Activity of HK853 by Luteolin. Zhou Y, Huang L, Ji S, Hou S, Luo L, Li C, Liu M, Liu Y, Jiang L. Molecules 24 E933 (2019)
  11. Imatinib can act as an Allosteric Activator of Abl Kinase. Xie T, Saleh T, Rossi P, Miller D, Kalodimos CG. J Mol Biol 434 167349 (2022)
  12. Modulation of conformational equilibrium by phosphorylation underlies the activation of deubiquitinase A. Kabra A, Rumpa E, Li Y. J Biol Chem 295 3945-3951 (2020)
  13. Allosteric regulation of autoinhibition and activation of c-Abl. Liu Y, Zhang M, Tsai CJ, Jang H, Nussinov R. Comput Struct Biotechnol J 20 4257-4270 (2022)
  14. Protein Flexibility and Dissociation Pathway Differentiation Can Explain Onset of Resistance Mutations in Kinases. Shekhar M, Smith Z, Seeliger MA, Tiwary P. Angew Chem Int Ed Engl 61 e202200983 (2022)
  15. Interface Residues That Drive Allosteric Transitions Also Control the Assembly of l-Lactate Dehydrogenase. Chen J, Thirumalai D. J Phys Chem B 122 11195-11205 (2018)
  16. Myristoyl's dual role in allosterically regulating and localizing Abl kinase. de Buhr S, Gräter F. Elife 12 e85216 (2023)
  17. The role of NMR in leveraging dynamics and entropy in drug design. Dubey A, Takeuchi K, Reibarkh M, Arthanari H. J Biomol NMR 74 479-498 (2020)
  18. Validation of an Allosteric Binding Site of Src Kinase Identified by Unbiased Ligand Binding Simulations. Mingione VR, Foda ZH, Paung Y, Philipose H, Rangwala AM, Shan Y, Seeliger MA. J Mol Biol 434 167628 (2022)
  19. A biophysical framework for double-drugging kinases. Kim C, Ludewig H, Hadzipasic A, Kutter S, Nguyen V, Kern D. Proc Natl Acad Sci U S A 120 e2304611120 (2023)
  20. Adding Substituent Nonadditivity in Protein Allostery by NMR. Clay MC, Kalodimos CG. Biophys J 119 1043-1044 (2020)
  21. Structural versatility that serves the function of the HRD motif in the catalytic loop of protein tyrosine kinase, Src. Cui Y, Sun G. Protein Sci 28 533-542 (2019)


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