Intermolecular Interactions Underlie Protein/peptide Phase Separation Irrespective of Sequence and Structure at Crowded Milieu

Overview

Journal Nat Commun

Specialty Biology

Date 2023 Oct 4

PMID 37794023

Authors

Manisha Poudyal

Komal Patel

Laxmikant Gadhe

Ajay Singh Sawner

Pradeep Kadu

Debalina Datta

Semanti Mukherjee

Soumik Ray

Ambuja Navalkar

Siddhartha Maiti

Debdeep Chatterjee

Jyoti Devi

Riya Bera

Nitisha Gahlot

Jennifer Joseph

Ranjith Padinhateeri

Samir K Maji

Affiliations

Soon will be listed here.

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.

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