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Phase Separation in Molecular Biology

A special issue of Molecules (ISSN 1420-3049). This special issue belongs to the section "Chemical Biology".

Deadline for manuscript submissions: 31 July 2024 | Viewed by 1542

Special Issue Editors


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Guest Editor
Department of Cell and Molecular Biology, St. Jude Children's Research Hospital, Memphis, TN 38105, USA
Interests: phase separation; chromatin biology; genome organization; biochemistry; biophysics

E-Mail Website
Guest Editor
Department of Structural Biology, St. Jude Children’s Research Hospital, Memphis, TN 38105, USA
Interests: phase separation; structural biology; fluorescence; biochemistry; biophysics

Special Issue Information

Dear Colleagues,

Phase separation of biological macromolecules can form sub-organellar cellular compartments called biomolecular condensates. These compartments can play diverse roles, but a growing body of evidence suggests they often function as membrane-less organelles, controlling cellular biochemistry through spatial concentration of specific components. The assembly of biomolecular condensates through phase separation relies on molecules with multivalent architecture, which form not a stoichiometrically defined higher-order complex, but networks of interaction. Multivalency can be encoded into macromolecules through repeats of structured domains, short motifs in intrinsically disordered regions, and charge-driven complexation. Depending on the lifetime of these interactions, or sites of valency, biomolecular condensates can have diverse material properties—from dynamic fluids to more static gels—which may afford diverse functionality to cellular compartments that are organized in this fashion.

While this framework of understanding for biomolecular condensates has arrived at a rapid pace, many questions remain. In this Special Issue, we focus on the following topics:

  • Outline of the structural and molecular biology of phase-separated biomolecular condensates both in vitro and in cells;
  • Assessment of ensembles and interactions adopted by intrinsically disordered proteins using simulations and experimentation;
  • Advances in methodology used to study biomolecular condensates;
  • Design and use of small molecules to target phase separation in disease;
  • Engineering of natural and synthetic condensates to probe how their macroscopic features emerge from small-scale interactions.

Dr. Bryan A. Gibson
Dr. Bappaditya Chandra
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Molecules is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2700 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • phase separation
  • membrane-less organelles
  • biomolecular condensates
  • intrinsically disordered proteins
  • multivalent interactions
  • transcription

Published Papers (1 paper)

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Research

26 pages, 9507 KiB  
Article
A Two-Step Mechanism for Creating Stable, Condensed Chromatin with the Polycomb Complex PRC1
by Elias Seif and Nicole J. Francis
Molecules 2024, 29(2), 323; https://doi.org/10.3390/molecules29020323 - 9 Jan 2024
Viewed by 1180
Abstract
The Drosophila PRC1 complex regulates gene expression by modifying histone proteins and chromatin architecture. Two PRC1 subunits, PSC and Ph, are most implicated in chromatin architecture. In vitro, PRC1 compacts chromatin and inhibits transcription and nucleosome remodeling. The long disordered C-terminal region of [...] Read more.
The Drosophila PRC1 complex regulates gene expression by modifying histone proteins and chromatin architecture. Two PRC1 subunits, PSC and Ph, are most implicated in chromatin architecture. In vitro, PRC1 compacts chromatin and inhibits transcription and nucleosome remodeling. The long disordered C-terminal region of PSC (PSC-CTR) is important for these activities, while Ph has little effect. In cells, Ph is important for condensate formation, long-range chromatin interactions, and gene regulation, and its polymerizing sterile alpha motif (SAM) is implicated in these activities. In vitro, truncated Ph containing the SAM and two other conserved domains (mini-Ph) undergoes phase separation with chromatin, suggesting a mechanism for SAM-dependent condensate formation in vivo. How the distinct activities of PSC and Ph on chromatin function together in PRC1 is not known. To address this question, we analyzed structures formed with large chromatin templates and PRC1 in vitro. PRC1 bridges chromatin into extensive fibrillar networks. Ph, its SAM, and SAM polymerization activity have little effect on these structures. Instead, the PSC-CTR controls their growth, and is sufficient for their formation. To understand how phase separation driven by Ph SAM intersects with the chromatin bridging activity of the PSC-CTR, we used mini-Ph to form condensates with chromatin and then challenged them with PRC1 lacking Ph (PRC1ΔPh). PRC1ΔPh converts mini-Ph chromatin condensates into clusters of small non-fusing condensates and bridged fibers. These condensates retain a high level of chromatin compaction and do not intermix. Thus, phase separation of chromatin by mini-Ph, followed by the action of the PSC-CTR, creates a unique chromatin organization with regions of high nucleosome density and extraordinary stability. We discuss how this coordinated sequential activity of two proteins found in the same complex may occur and the possible implications of stable chromatin architectures in maintaining transcription states. Full article
(This article belongs to the Special Issue Phase Separation in Molecular Biology)
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