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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
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    2. 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.

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