IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v13y2022i1d10.1038_s41467-022-31215-5.html
   My bibliography  Save this article

Mapping the conformational energy landscape of Abl kinase using ClyA nanopore tweezers

Author

Listed:
  • Fanjun Li

    (University of Massachusetts Amherst)

  • Monifa A. Fahie

    (University of Massachusetts Amherst)

  • Kaitlyn M. Gilliam

    (University of Massachusetts Amherst)

  • Ryan Pham

    (University of Massachusetts Amherst)

  • Min Chen

    (University of Massachusetts Amherst
    University of Massachusetts Amherst)

Abstract

Protein kinases play central roles in cellular regulation by catalyzing the phosphorylation of target proteins. Kinases have inherent structural flexibility allowing them to switch between active and inactive states. Quantitative characterization of kinase conformational dynamics is challenging. Here, we use nanopore tweezers to assess the conformational dynamics of Abl kinase domain, which is shown to interconvert between two major conformational states where one conformation comprises three sub-states. Analysis of kinase-substrate and kinase-inhibitor interactions uncovers the functional roles of relevant states and enables the elucidation of the mechanism underlying the catalytic deficiency of an inactive Abl mutant G321V. Furthermore, we obtain the energy landscape of Abl kinase by quantifying the population and transition rates of the conformational states. These results extend the view on the dynamic nature of Abl kinase and suggest nanopore tweezers can be used as an efficient tool for other members of the human kinome.

Suggested Citation

  • Fanjun Li & Monifa A. Fahie & Kaitlyn M. Gilliam & Ryan Pham & Min Chen, 2022. "Mapping the conformational energy landscape of Abl kinase using ClyA nanopore tweezers," Nature Communications, Nature, vol. 13(1), pages 1-10, December.
    • Handle: RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-022-31215-5
    DOI: 10.1038/s41467-022-31215-5
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/s41467-022-31215-5
    File Function: Abstract
    Download Restriction: no
    File URL: https://libkey.io/10.1038/s41467-022-31215-5?utm_source=ideas
    LibKey link: if access is restricted and if your library uses this service, LibKey will redirect you to where you can use your library subscription to access this item
    ---><---

    References listed on IDEAS

    as
    1. Doeke R. Hekstra & K. Ian White & Michael A. Socolich & Robert W. Henning & Vukica Šrajer & Rama Ranganathan, 2016. "Electric-field-stimulated protein mechanics," Nature, Nature, vol. 540(7633), pages 400-405, December.
    2. Diwakar Shukla & Yilin Meng & Benoît Roux & Vijay S. Pande, 2014. "Activation pathway of Src kinase reveals intermediate states as targets for drug design," Nature Communications, Nature, vol. 5(1), pages 1-11, May.
    3. Nicole Stéphanie Galenkamp & Misha Soskine & Jos Hermans & Carsten Wloka & Giovanni Maglia, 2018. "Direct electrical quantification of glucose and asparagine from bodily fluids using nanopores," Nature Communications, Nature, vol. 9(1), pages 1-8, December.
    4. Jianming Zhang & Francisco J. Adrián & Wolfgang Jahnke & Sandra W. Cowan-Jacob & Allen G. Li & Roxana E. Iacob & Taebo Sim & John Powers & Christine Dierks & Fangxian Sun & Gui-Rong Guo & Qiang Ding &, 2010. "Targeting Bcr–Abl by combining allosteric with ATP-binding-site inhibitors," Nature, Nature, vol. 463(7280), pages 501-506, January.
    5. Andrew A. Wylie & Joseph Schoepfer & Wolfgang Jahnke & Sandra W. Cowan-Jacob & Alice Loo & Pascal Furet & Andreas L. Marzinzik & Xavier Pelle & Jerry Donovan & Wenjing Zhu & Silvia Buonamici & A. Quam, 2017. "The allosteric inhibitor ABL001 enables dual targeting of BCR–ABL1," Nature, Nature, vol. 543(7647), pages 733-737, March.
    Full references (including those not matched with items on IDEAS)

    Citations

    Citations are extracted by the CitEc Project, subscribe to its RSS feed for this item.
    as


    Cited by:

    1. Ki-Baek Jeong & Minju Ryu & Jin-Sik Kim & Minsoo Kim & Jejoong Yoo & Minji Chung & Sohee Oh & Gyunghee Jo & Seong-Gyu Lee & Ho Min Kim & Mi-Kyung Lee & Seung-Wook Chi, 2023. "Single-molecule fingerprinting of protein-drug interaction using a funneled biological nanopore," Nature Communications, Nature, vol. 14(1), pages 1-14, December.

    Most related items

    These are the items that most often cite the same works as this one and are cited by the same works as this one.
    1. Tyler S. Beyett & Ciric To & David E. Heppner & Jaimin K. Rana & Anna M. Schmoker & Jaebong Jang & Dries J. H. Clercq & Gabriel Gomez & David A. Scott & Nathanael S. Gray & Pasi A. Jänne & Michael J. , 2022. "Molecular basis for cooperative binding and synergy of ATP-site and allosteric EGFR inhibitors," Nature Communications, Nature, vol. 13(1), pages 1-11, December.
    2. Trayder Thomas & Benoît Roux, 2021. "Tyrosine kinases: complex molecular systems challenging computational methodologies," The European Physical Journal B: Condensed Matter and Complex Systems, Springer;EDP Sciences, vol. 94(10), pages 1-13, October.
    3. Yanghang Pan & Xinzhu Wang & Weiyang Zhang & Lingyu Tang & Zhangyan Mu & Cheng Liu & Bailin Tian & Muchun Fei & Yamei Sun & Huanhuan Su & Libo Gao & Peng Wang & Xiangfeng Duan & Jing Ma & Mengning Din, 2022. "Boosting the performance of single-atom catalysts via external electric field polarization," Nature Communications, Nature, vol. 13(1), pages 1-12, December.
    4. Jianxin Yang & Tianle Pan & Zhenming Xie & Wu Yuan & Ho-Pui Ho, 2024. "In-tube micro-pyramidal silicon nanopore for inertial-kinetic sensing of single molecules," Nature Communications, Nature, vol. 15(1), pages 1-12, December.
    5. Ki-Baek Jeong & Minju Ryu & Jin-Sik Kim & Minsoo Kim & Jejoong Yoo & Minji Chung & Sohee Oh & Gyunghee Jo & Seong-Gyu Lee & Ho Min Kim & Mi-Kyung Lee & Seung-Wook Chi, 2023. "Single-molecule fingerprinting of protein-drug interaction using a funneled biological nanopore," Nature Communications, Nature, vol. 14(1), pages 1-14, December.
    6. Eugene Klyshko & Justin Sung-Ho Kim & Lauren McGough & Victoria Valeeva & Ethan Lee & Rama Ranganathan & Sarah Rauscher, 2024. "Functional protein dynamics in a crystal," Nature Communications, Nature, vol. 15(1), pages 1-13, December.
    7. Arango-Restrepo, A. & Rubi, J.M. & Barragán, D., 2018. "Kinetics and energetics of chemical reactions through intermediate states," Physica A: Statistical Mechanics and its Applications, Elsevier, vol. 509(C), pages 86-96.
    8. Anh T. P. Nguyen & Austin T. Weigle & Diwakar Shukla, 2024. "Functional regulation of aquaporin dynamics by lipid bilayer composition," Nature Communications, Nature, vol. 15(1), pages 1-19, December.
    9. Lauren Ashley Mayse & Ali Imran & Motahareh Ghahari Larimi & Michael S. Cosgrove & Aaron James Wolfe & Liviu Movileanu, 2022. "Disentangling the recognition complexity of a protein hub using a nanopore," Nature Communications, Nature, vol. 13(1), pages 1-11, December.
    10. Pelin Ayaz & Agatha Lyczek & YiTing Paung & Victoria R. Mingione & Roxana E. Iacob & Parker W. Waal & John R. Engen & Markus A. Seeliger & Yibing Shan & David E. Shaw, 2023. "Structural mechanism of a drug-binding process involving a large conformational change of the protein target," Nature Communications, Nature, vol. 14(1), pages 1-15, December.
    11. Kevin M. Dalton & Jack B. Greisman & Doeke R. Hekstra, 2022. "A unifying Bayesian framework for merging X-ray diffraction data," Nature Communications, Nature, vol. 13(1), pages 1-13, December.
    12. Mingyu Li & Xiaobing Lan & Xinchao Shi & Chunhao Zhu & Xun Lu & Jun Pu & Shaoyong Lu & Jian Zhang, 2024. "Delineating the stepwise millisecond allosteric activation mechanism of the class C GPCR dimer mGlu5," Nature Communications, Nature, vol. 15(1), pages 1-14, December.

    More about this item

    Statistics

    Access and download statistics

    Corrections

    All material on this site has been provided by the respective publishers and authors. You can help correct errors and omissions. When requesting a correction, please mention this item's handle: RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-022-31215-5. See general information about how to correct material in RePEc.

    If you have authored this item and are not yet registered with RePEc, we encourage you to do it here. This allows to link your profile to this item. It also allows you to accept potential citations to this item that we are uncertain about.

    If CitEc recognized a bibliographic reference but did not link an item in RePEc to it, you can help with this form .

    If you know of missing items citing this one, you can help us creating those links by adding the relevant references in the same way as above, for each refering item. If you are a registered author of this item, you may also want to check the "citations" tab in your RePEc Author Service profile, as there may be some citations waiting for confirmation.

    For technical questions regarding this item, or to correct its authors, title, abstract, bibliographic or download information, contact: Sonal Shukla or Springer Nature Abstracting and Indexing (email available below). General contact details of provider: http://www.nature.com .

    Please note that corrections may take a couple of weeks to filter through the various RePEc services.

    IDEAS is a RePEc service. RePEc uses bibliographic data supplied by the respective publishers.