IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v14y2023i1d10.1038_s41467-023-41864-9.html
   My bibliography  Save this article

Intermolecular interactions underlie protein/peptide phase separation irrespective of sequence and structure at crowded milieu

Author

Listed:
  • Manisha Poudyal

    (IIT Bombay, Powai)

  • Komal Patel

    (IIT Bombay, Powai
    IIT Bombay, Powai)

  • Laxmikant Gadhe

    (IIT Bombay, Powai)

  • Ajay Singh Sawner

    (IIT Bombay, Powai)

  • Pradeep Kadu

    (IIT Bombay, Powai)

  • Debalina Datta

    (IIT Bombay, Powai)

  • Semanti Mukherjee

    (IIT Bombay, Powai)

  • Soumik Ray

    (IIT Bombay, Powai)

  • Ambuja Navalkar

    (IIT Bombay, Powai)

  • Siddhartha Maiti

    (IIT Bombay, Powai
    VIT Bhopal University)

  • Debdeep Chatterjee

    (IIT Bombay, Powai)

  • Jyoti Devi

    (IIT Bombay, Powai)

  • Riya Bera

    (IIT Bombay, Powai)

  • Nitisha Gahlot

    (IIT Bombay, Powai)

  • Jennifer Joseph

    (IIT Bombay, Powai)

  • Ranjith Padinhateeri

    (IIT Bombay, Powai)

  • Samir K. Maji

    (IIT Bombay, Powai
    IIT Bombay, Powai)

Abstract

Liquid-liquid phase separation (LLPS) has emerged as a crucial biological phenomenon underlying the sequestration of macromolecules (such as proteins and nucleic acids) into membraneless organelles in cells. Unstructured and intrinsically disordered domains are known to facilitate multivalent interactions driving protein LLPS. We hypothesized that LLPS could be an intrinsic property of proteins/polypeptides but with distinct phase regimes irrespective of their sequence and structure. To examine this, we studied many (a total of 23) proteins/polypeptides with different structures and sequences for LLPS study in the presence and absence of molecular crowder, polyethylene glycol (PEG-8000). We showed that all proteins and even highly charged polypeptides (under study) can undergo liquid condensate formation, however with different phase regimes and intermolecular interactions. We further demonstrated that electrostatic, hydrophobic, and H-bonding or a combination of such intermolecular interactions plays a crucial role in individual protein/peptide LLPS.

Suggested Citation

  • Manisha Poudyal & Komal Patel & Laxmikant Gadhe & Ajay Singh Sawner & Pradeep Kadu & Debalina Datta & Semanti Mukherjee & Soumik Ray & Ambuja Navalkar & Siddhartha Maiti & Debdeep Chatterjee & Jyoti D, 2023. "Intermolecular interactions underlie protein/peptide phase separation irrespective of sequence and structure at crowded milieu," Nature Communications, Nature, vol. 14(1), pages 1-21, December.
    • Handle: RePEc:nat:natcom:v:14:y:2023:i:1:d:10.1038_s41467-023-41864-9
    DOI: 10.1038/s41467-023-41864-9
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/s41467-023-41864-9
    File Function: Abstract
    Download Restriction: no
    File URL: https://libkey.io/10.1038/s41467-023-41864-9?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. Adam G. Larson & Daniel Elnatan & Madeline M. Keenen & Michael J. Trnka & Jonathan B. Johnston & Alma L. Burlingame & David A. Agard & Sy Redding & Geeta J. Narlikar, 2017. "Liquid droplet formation by HP1α suggests a role for phase separation in heterochromatin," Nature, Nature, vol. 547(7662), pages 236-240, July.
    2. Rachel S. Fisher & Shana Elbaum-Garfinkle, 2020. "Tunable multiphase dynamics of arginine and lysine liquid condensates," Nature Communications, Nature, vol. 11(1), pages 1-10, December.
    3. Ho Yin Chan & Vassiliy Lubchenko, 2019. "A mechanism for reversible mesoscopic aggregation in liquid solutions," Nature Communications, Nature, vol. 10(1), pages 1-11, December.
    4. Premchand Rajeev & Nivedita Singh & Adel Kechkar & Corey Butler & Narendrakumar Ramanan & Jean-Baptiste Sibarita & Mini Jose & Deepak Nair, 2022. "Nanoscale regulation of Ca2+ dependent phase transitions and real-time dynamics of SAP97/hDLG," Nature Communications, Nature, vol. 13(1), pages 1-18, December.
    5. Hermann Broder Schmidt & Ariana Barreau & Rajat Rohatgi, 2019. "Phase separation-deficient TDP43 remains functional in splicing," Nature Communications, Nature, vol. 10(1), pages 1-14, December.
    6. Susmitha Ambadipudi & Jacek Biernat & Dietmar Riedel & Eckhard Mandelkow & Markus Zweckstetter, 2017. "Liquid–liquid phase separation of the microtubule-binding repeats of the Alzheimer-related protein Tau," Nature Communications, Nature, vol. 8(1), pages 1-13, December.
    7. Joshua A. Riback & Lian Zhu & Mylene C. Ferrolino & Michele Tolbert & Diana M. Mitrea & David W. Sanders & Ming-Tzo Wei & Richard W. Kriwacki & Clifford P. Brangwynne, 2020. "Composition-dependent thermodynamics of intracellular phase separation," Nature, Nature, vol. 581(7807), pages 209-214, May.
    8. Martin Falk & Yana Feodorova & Natalia Naumova & Maxim Imakaev & Bryan R. Lajoie & Heinrich Leonhardt & Boris Joffe & Job Dekker & Geoffrey Fudenberg & Irina Solovei & Leonid A. Mirny, 2019. "Heterochromatin drives compartmentalization of inverted and conventional nuclei," Nature, Nature, vol. 570(7761), pages 395-399, June.
    9. Pilong Li & Sudeep Banjade & Hui-Chun Cheng & Soyeon Kim & Baoyu Chen & Liang Guo & Marc Llaguno & Javoris V. Hollingsworth & David S. King & Salman F. Banani & Paul S. Russo & Qiu-Xing Jiang & B. Tra, 2012. "Phase transitions in the assembly of multivalent signalling proteins," Nature, Nature, vol. 483(7389), pages 336-340, March.
    10. Martin Falk & Yana Feodorova & Natalia Naumova & Maxim Imakaev & Bryan R. Lajoie & Heinrich Leonhardt & Boris Joffe & Job Dekker & Geoffrey Fudenberg & Irina Solovei & Leonid A. Mirny, 2019. "Publisher Correction: Heterochromatin drives compartmentalization of inverted and conventional nuclei," Nature, Nature, vol. 572(7771), pages 22-22, August.
    11. Erik W. Martin & Tyler S. Harmon & Jesse B. Hopkins & Srinivas Chakravarthy & J. Jeremías Incicco & Peter Schuck & Andrea Soranno & Tanja Mittag, 2021. "A multi-step nucleation process determines the kinetics of prion-like domain phase separation," Nature Communications, Nature, vol. 12(1), pages 1-12, December.
    12. Georg Krainer & Timothy J. Welsh & Jerelle A. Joseph & Jorge R. Espinosa & Sina Wittmann & Ella Csilléry & Akshay Sridhar & Zenon Toprakcioglu & Giedre Gudiškytė & Magdalena A. Czekalska & William E. , 2021. "Reentrant liquid condensate phase of proteins is stabilized by hydrophobic and non-ionic interactions," Nature Communications, Nature, vol. 12(1), pages 1-14, December.
    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. Shuang Hou & Jiaojiao Hu & Zhaowei Yu & Dan Li & Cong Liu & Yong Zhang, 2024. "Machine learning predictor PSPire screens for phase-separating proteins lacking intrinsically disordered regions," Nature Communications, Nature, vol. 15(1), pages 1-13, 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. Andrew Z. Lin & Kiersten M. Ruff & Furqan Dar & Ameya Jalihal & Matthew R. King & Jared M. Lalmansingh & Ammon E. Posey & Nadia A. Erkamp & Ian Seim & Amy S. Gladfelter & Rohit V. Pappu, 2023. "Dynamical control enables the formation of demixed biomolecular condensates," Nature Communications, Nature, vol. 14(1), pages 1-17, December.
    2. Andres R. Tejedor & Ignacio Sanchez-Burgos & Maria Estevez-Espinosa & Adiran Garaizar & Rosana Collepardo-Guevara & Jorge Ramirez & Jorge R. Espinosa, 2022. "Protein structural transitions critically transform the network connectivity and viscoelasticity of RNA-binding protein condensates but RNA can prevent it," Nature Communications, Nature, vol. 13(1), pages 1-15, December.
    3. Ziad Ibrahim & Tao Wang & Olivier Destaing & Nicola Salvi & Naghmeh Hoghoughi & Clovis Chabert & Alexandra Rusu & Jinjun Gao & Leonardo Feletto & Nicolas Reynoird & Thomas Schalch & Yingming Zhao & Ma, 2022. "Structural insights into p300 regulation and acetylation-dependent genome organisation," Nature Communications, Nature, vol. 13(1), pages 1-23, December.
    4. Taehyun Kim & Jaeyoon Yoo & Sungho Do & Dong Soo Hwang & YongKeun Park & Yongdae Shin, 2023. "RNA-mediated demixing transition of low-density condensates," Nature Communications, Nature, vol. 14(1), pages 1-15, December.
    5. Daniel C. Carrettiero & Maria C. Almeida & Andrew P. Longhini & Jennifer N. Rauch & Dasol Han & Xuemei Zhang & Saeed Najafi & Jason E. Gestwicki & Kenneth S. Kosik, 2022. "Stress routes clients to the proteasome via a BAG2 ubiquitin-independent degradation condensate," Nature Communications, Nature, vol. 13(1), pages 1-16, December.
    6. Zheng Shen & Daxiao Sun & Adriana Savastano & Sára Joana Varga & Maria-Sol Cima-Omori & Stefan Becker & Alf Honigmann & Markus Zweckstetter, 2023. "Multivalent Tau/PSD-95 interactions arrest in vitro condensates and clusters mimicking the postsynaptic density," Nature Communications, Nature, vol. 14(1), pages 1-13, December.
    7. Ting Peng & Yingping Hou & Haowei Meng & Yong Cao & Xiaotian Wang & Lumeng Jia & Qing Chen & Yang Zheng & Yujie Sun & Hebing Chen & Tingting Li & Cheng Li, 2023. "Mapping nucleolus-associated chromatin interactions using nucleolus Hi-C reveals pattern of heterochromatin interactions," Nature Communications, Nature, vol. 14(1), pages 1-15, December.
    8. Vinícius G. Contessoto & Olga Dudchenko & Erez Lieberman Aiden & Peter G. Wolynes & José N. Onuchic & Michele Pierro, 2023. "Interphase chromosomes of the Aedes aegypti mosquito are liquid crystalline and can sense mechanical cues," Nature Communications, Nature, vol. 14(1), pages 1-12, December.
    9. Avigail Baruch Leshem & Sian Sloan-Dennison & Tlalit Massarano & Shavit Ben-David & Duncan Graham & Karen Faulds & Hugo E. Gottlieb & Jordan H. Chill & Ayala Lampel, 2023. "Biomolecular condensates formed by designer minimalistic peptides," Nature Communications, Nature, vol. 14(1), pages 1-11, December.
    10. Mina Farag & Wade M. Borcherds & Anne Bremer & Tanja Mittag & Rohit V. Pappu, 2023. "Phase separation of protein mixtures is driven by the interplay of homotypic and heterotypic interactions," Nature Communications, Nature, vol. 14(1), pages 1-16, December.
    11. Yuri Hong & Saeed Najafi & Thomas Casey & Joan-Emma Shea & Song-I Han & Dong Soo Hwang, 2022. "Hydrophobicity of arginine leads to reentrant liquid-liquid phase separation behaviors of arginine-rich proteins," Nature Communications, Nature, vol. 13(1), pages 1-15, December.
    12. Tengfei Wang & Shuxiang Shi & Yuanyuan Shi & Peipei Jiang & Ganlu Hu & Qinying Ye & Zhan Shi & Kexin Yu & Chenguang Wang & Guoping Fan & Suwen Zhao & Hanhui Ma & Alex C. Y. Chang & Zhi Li & Qian Bian , 2023. "Chemical-induced phase transition and global conformational reorganization of chromatin," Nature Communications, Nature, vol. 14(1), pages 1-18, December.
    13. Aishwarya Agarwal & Lisha Arora & Sandeep K. Rai & Anamika Avni & Samrat Mukhopadhyay, 2022. "Spatiotemporal modulations in heterotypic condensates of prion and α-synuclein control phase transitions and amyloid conversion," Nature Communications, Nature, vol. 13(1), pages 1-14, December.
    14. Hye Ji Cha & Özgün Uyan & Yan Kai & Tianxin Liu & Qian Zhu & Zuzana Tothova & Giovanni A. Botten & Jian Xu & Guo-Cheng Yuan & Job Dekker & Stuart H. Orkin, 2021. "Inner nuclear protein Matrin-3 coordinates cell differentiation by stabilizing chromatin architecture," Nature Communications, Nature, vol. 12(1), pages 1-19, December.
    15. William E. Arter & Runzhang Qi & Nadia A. Erkamp & Georg Krainer & Kieran Didi & Timothy J. Welsh & Julia Acker & Jonathan Nixon-Abell & Seema Qamar & Jordina Guillén-Boixet & Titus M. Franzmann & Dav, 2022. "Biomolecular condensate phase diagrams with a combinatorial microdroplet platform," Nature Communications, Nature, vol. 13(1), pages 1-10, December.
    16. Pan Jia & Xiang Li & Xuelei Wang & Liangjiao Yao & Yingying Xu & Yu Hu & Wenwen Xu & Zhe He & Qifan Zhao & Yicong Deng & Yi Zang & Meiyu Zhang & Yan Zhang & Jun Qin & Wei Lu, 2021. "ZMYND8 mediated liquid condensates spatiotemporally decommission the latent super-enhancers during macrophage polarization," Nature Communications, Nature, vol. 12(1), pages 1-17, December.
    17. Agustín Mangiarotti & Nannan Chen & Ziliang Zhao & Reinhard Lipowsky & Rumiana Dimova, 2023. "Wetting and complex remodeling of membranes by biomolecular condensates," Nature Communications, Nature, vol. 14(1), pages 1-15, December.
    18. Tuan Nguyen & Sai Li & Jeremy T-H Chang & John W. Watters & Htet Ng & Adewola Osunsade & Yael David & Shixin Liu, 2022. "Chromatin sequesters pioneer transcription factor Sox2 from exerting force on DNA," Nature Communications, Nature, vol. 13(1), pages 1-11, December.
    19. Sangram Kadam & Kiran Kumari & Vinoth Manivannan & Shuvadip Dutta & Mithun K. Mitra & Ranjith Padinhateeri, 2023. "Predicting scale-dependent chromatin polymer properties from systematic coarse-graining," Nature Communications, Nature, vol. 14(1), pages 1-14, December.
    20. Archishman Ghosh & Divya Kota & Huan-Xiang Zhou, 2021. "Shear relaxation governs fusion dynamics of biomolecular condensates," Nature Communications, Nature, vol. 12(1), pages 1-10, 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:14:y:2023:i:1:d:10.1038_s41467-023-41864-9. 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.