Roshan Mammen Regy
Current Organizations / Institutes
The organizations/institutes from the scholar's latest article
Roshan Mammen Regy has a total of 21 co-authors. Here are the top co-authors by number of shared publications:
- Jeetain Mittal
Artie McFerrin Department of Chemical Engineering, Texas A&M University, College Station, TX, USA
2 shared publications - Amy Henrickson
Department of Chemistry and Biochemistry, University of Lethbridge, Lethbridge, Alberta T1K 3M4, Canada
1 shared publication Andrea J. Mendiola
Midwestern University
1 shared publication- Ashish Bihani
CSIR - Centre for Cellular and Molecular Biology (CCMB), Hyderabad, India
1 shared publication - Benjamin S. Schuster
Department of Chemical and Biochemical Engineering, Rutgers, The State University of New Jersey, Piscataway, USA
1 shared publication - Borries Demeler
Department of Chemistry and Biochemistry, University of Montana, Missoula, USA
1 shared publication
Latest Publications
- Open Access
How a disordered linker in the Polycomb protein Polyhomeotic tunes phase separation and oligomerization
Biomolecular condensates are increasingly appreciated for their function in organizing and regulating biochemical processes in cells, including chromatin function. Condensate formation and properties are encoded in protein sequence but the mechanisms linking sequence to macroscale properties are incompletely understood. Cross species comparisons can reveal mechanisms either because they identify conserved functions or because they point to important differences. Here we use in vitro reconstitution and molecular dynamics simulations to compare Drosophila and human sequences that regulate condensate formation driven by the sterile alpha motif (SAM) oligomerization domain in the Polyhomeotic (Ph) subunit of the chromatin regulatory complex PRC1. We discover evolutionarily diverged contacts between the conserved SAM and the disordered linker that connects it to the rest of Ph. Linker-SAM interactions increase oligomerization and regulate formation and properties of reconstituted condensates. Oligomerization affects condensate dynamics but, in most cases, has little effect on their formation. Linker-SAM interactions also affect condensate formation in Drosophila and human cells, and growth in Drosophila imaginal discs. Our data show how evolutionary sequence changes in linkers connecting conserved structured domains can alter condensate properties.
Open AccessHow a disordered linker in the Polycomb protein Polyhomeotic tunes phase separation and oligomerization
Biomolecular condensates are increasingly appreciated for their function in organizing and regulating biochemical processes in cells, including chromatin function. Condensate formation and properties are encoded in protein sequence but the mechanisms linking sequence to macroscale properties are incompletely understood. Cross species comparisons can reveal mechanisms either because they identify conserved functions or because they point to important differences. Here we use in vitro reconstitution and molecular dynamics simulations to compare Drosophila and human sequences that regulate condensate formation driven by the sterile alpha motif (SAM) oligomerization domain in the Polyhomeotic (Ph) subunit of the chromatin regulatory complex PRC1. We discover evolutionarily diverged contacts between the conserved SAM and the disordered linker that connects it to the rest of Ph. Linker-SAM interactions increase oligomerization and regulate formation and properties of reconstituted condensates. Oligomerization affects condensate dynamics but, in most cases, has little effect on their formation. Linker-SAM interactions also affect condensate formation in Drosophila and human cells, and growth in Drosophila imaginal discs. Our data show how evolutionary sequence changes in linkers connecting conserved structured domains can alter condensate properties.
- Open Access
Amphiphilic proteins coassemble into multiphasic condensates and act as biomolecular surfactants
Cells contain membraneless compartments that assemble due to liquid-liquid phase separation, including biomolecular condensates with complex morphologies. For instance, certain condensates are surrounded by a film of distinct composition, such as Ape1 condensates coated by a layer of Atg19, required for selective autophagy in yeast. Other condensates are multiphasic, with nested liquid phases of distinct compositions and functions, such as in the case of ribosome biogenesis in the nucleolus. The size and structure of such condensates must be regulated for proper biological function. We leveraged a bio-inspired approach to discover how amphiphilic, surfactant-like proteins may contribute to the structure and size regulation of biomolecular condensates. We designed and examined families of amphiphilic proteins comprising one phase-separating domain and one non-phase separating domain. In particular, these proteins contain the soluble structured domain glutathione S-transferase (GST) or maltose binding protein (MBP), fused to the intrinsically disordered RGG domain from P granule protein LAF-1. When one amphiphilic protein is mixed in vitro with RGG-RGG, the proteins assemble into enveloped condensates, with RGG-RGG at the core, and the amphiphilic protein forming the surface film layer. Importantly, we found that MBP-based amphiphiles are surfactants and control droplet size, with increasing surfactant concentration resulting in smaller droplet radii. In contrast, GST-based amphiphiles at increased concentrations co-assemble with RGG-RGG into multiphasic structures. We propose a mechanism for these experimental observations, supported by molecular simulations of a minimalist model. We speculate that surfactant proteins may play a significant role in regulating the structure and function of biomolecular condensates.
Open AccessAmphiphilic proteins coassemble into multiphasic condensates and act as biomolecular surfactants
Cells contain membraneless compartments that assemble due to liquid-liquid phase separation, including biomolecular condensates with complex morphologies. For instance, certain condensates are surrounded by a film of distinct composition, such as Ape1 condensates coated by a layer of Atg19, required for selective autophagy in yeast. Other condensates are multiphasic, with nested liquid phases of distinct compositions and functions, such as in the case of ribosome biogenesis in the nucleolus. The size and structure of such condensates must be regulated for proper biological function. We leveraged a bio-inspired approach to discover how amphiphilic, surfactant-like proteins may contribute to the structure and size regulation of biomolecular condensates. We designed and examined families of amphiphilic proteins comprising one phase-separating domain and one non-phase separating domain. In particular, these proteins contain the soluble structured domain glutathione S-transferase (GST) or maltose binding protein (MBP), fused to the intrinsically disordered RGG domain from P granule protein LAF-1. When one amphiphilic protein is mixed in vitro with RGG-RGG, the proteins assemble into enveloped condensates, with RGG-RGG at the core, and the amphiphilic protein forming the surface film layer. Importantly, we found that MBP-based amphiphiles are surfactants and control droplet size, with increasing surfactant concentration resulting in smaller droplet radii. In contrast, GST-based amphiphiles at increased concentrations co-assemble with RGG-RGG into multiphasic structures. We propose a mechanism for these experimental observations, supported by molecular simulations of a minimalist model. We speculate that surfactant proteins may play a significant role in regulating the structure and function of biomolecular condensates.