Jeetain Mittal

Molecular Origins of pH Gradients in Charge-Regulated Biomolecular Condensates

The paper introduces a computational framework to model pH gradients in biomolecular condensates and shows sequence-dependent pH shifts in FUS and PGL-3.

Scaffold Affinity Tunes Biomolecular Condensate Function

This study shows that scaffold binding affinity determines condensate phase behavior, dynamics, and biochemical output in vitro and in human cells.

Condensate Material Properties Influence Cargo Selection for Neuronal Extrusion via Large Extracellular Exopher Vesicles

The paper investigates how condensate material properties affect exopher cargo selection in neurons, finding that gel-like condensates are more efficiently recruited than liquid-like ones.

The role of electrostatic interactions in the phase separation of HP1α and its protein binding partners

This study investigates how electrostatic interactions influence HP1α phase separation and its interactions with binding partners, showing that these interactions modulate HP1's properties and functions.

Biomolecular Condensates Act as Distinct Solvation Environments that Reshape Amino Acid pK Values

The paper investigates how biomolecular condensates alter amino acid pKa values through simulations, finding protonated states are favored in condensates.

Learning molecular determinants of selective small-molecule partitioning across biomolecular condensates

This paper develops a graph-based model to predict small-molecule partitioning into biomolecular condensates using existing experimental data and applies it to identify chemically diverse partitioners.

Endosome maturation is orchestrated by inside-out proton signaling through a Na+/H+ exchanger and pH-dependent Rab GTPase cycling

The paper shows that endosome maturation is regulated by proton signaling through NHE6 and pH-dependent Rab7 cycling, with implications for neurodegeneration.

Short RNA chaperones promote aggregation-resistant TDP-43 conformers to mitigate neurodegeneration

Short UG-rich RNAs bind and stabilize TDP-43 RNA-recognition motifs to allosterically destabilize its prion-like domain helical region, preventing aggregation and mitigating neurodegeneration in cells and mice.

Organization of core mitochondrial replication components into multiphasic condensates

The paper investigates how mitochondrial replication components form multiphasic condensates and shows how ssDNA and dsDNA are segregated by architectural proteins.

Breaking β-sheets in FUS prion-like domain preserves phase separation and function but prevents aggregation and toxicity

This study introduces β-sheet breaking proline residues into FUS prion-like domain to prevent aggregation and toxicity while preserving phase separation and function.

A High-Throughput, Flow Cytometry Approach to Measure Phase Behavior and Exchange in Biomolecular Condensates

This study develops a flow cytometry method to measure biomolecular condensate formation, colocalization, and exchange dynamics, revealing that condensate aging reduces molecular dynamics.

Sticky Interactions Govern Sequence-Dependent Dynamics in Biomolecular Condensates

This study uses molecular dynamics simulations to show that sequence-dependent electrostatic interactions govern condensate viscosity and diffusivity in IDPs.

The Structural Basis for RNA Binding and Recognition of the Disordered Prion-Like Domain of TDP-43

This paper investigates how the disordered C-terminal domain of TDP-43 interacts with RNA and identifies key residues and structural features that mediate RNA recognition and binding specificity.

Site-specific methionine oxidation alters structure and phase separation of TDP-43 C-terminal domain

This study shows methionine oxidation in TDP-43's C-terminal domain disrupts structure and phase separation through region-specific mechanisms.

RNA modulates FUS condensate assembly, dynamics, and aggregation through diverse molecular contacts

This study shows RNA modulates FUS condensate assembly and aggregation through specific molecular interactions, affecting phase separation and aggregate formation.

Structural details of helix-mediated TDP-43 C-terminal domain multimerization

This study investigates the structural basis of TDP-43 C-terminal domain multimerization using biophysical experiments, AlphaFold2-Multimer, and simulations, revealing helical oligomerization and the role of specific residues in phase separation and disease.

Multiscale simulations elucidate the mechanism of polyglutamine aggregation and the role of flanking domains in fibril polymorphism

This study uses multiscale simulations to investigate polyglutamine aggregation mechanisms and how the N17 flanking domain influences fibril polymorphism in Huntingtons disease.

Molecular Basis of EWS Interdomain Self-Association and Its Role in Condensate Formation

This paper investigates how EWS's RNA-binding domains interact with its low-complexity domain to influence condensate formation, revealing electrostatic and residue-specific interactions that underlie EWS self-association.

Multiphasic Organization and Differential Dynamics of Proteins Within Protein-DNA Biomolecular Condensates

This study uses a coarse-grained model to show DNA length and flexibility influence protein-DNA condensate structure and protein dynamics, revealing multiphasic organization and differential diffusion modes.

Elucidation of the molecular interaction network underlying full-length FUS conformational transitions and its phase separation using atomistic simulations

This study uses atomistic simulations to analyze the conformational dynamics and interdomain interactions of full-length FUS during phase separation, revealing key electrostatic interactions and domain stability effects.

Controlling Multicomponent Condensate Morphology via Additive-Modulated Interactions

This study uses simulations to show how small-molecule cosolutes alter condensate morphology by changing interaction strengths and stoichiometry.

Amino Acid Transfer Free Energies Reveal Thermodynamic Driving Forces in Biomolecular Condensate Formation

This study calculates amino acid transfer free energies to reveal thermodynamic contributions to biomolecular condensate formation, showing charge asymmetry and interactions between protein and water.

Heterotypic Protein Interactions Modulate the Condensate Dynamics and Aggregation of α-Synuclein

This study investigates how heterotypic protein interactions affect α-synuclein condensate dynamics and aggregation, showing that multivalent electrostatic interactions drive co-condensation and promote amyloid fibril formation.

Uncovering the molecular interactions underlying MBD2 and MBD3 phase separation

This study investigates the molecular interactions driving phase separation in MBD2 and MBD3 proteins, revealing distinct mechanisms despite their structural similarity.

Transient interdomain interactions modulate the monomeric structural ensemble and self-assembly of Huntingtin Exon 1

This study uses molecular dynamics simulations to show that transient interdomain interactions in Httex1 modulate its structural ensemble and self-assembly, contributing to aggregation in Huntington's disease.

Capturing the Conformational Heterogeneity of HSPB1 Chaperone Oligomers at Atomic Resolution

This paper characterizes the structure and dynamics of HSPB1 oligomers using biophysical and computational methods, revealing conformational heterogeneity and domain-specific interactions.

Sequence-encoded Spatiotemporal Dependence of Viscoelasticity of Protein Condensates Using Computational Microrheology

This paper introduces a computational microrheology technique to quantify sequence-dependent viscoelasticity of protein condensates formed by intrinsically disordered proteins.

Sequence dependent co-phase separation of RNA-protein mixtures elucidated using molecular simulations

The paper develops a coarse-grained RNA model to study RNA-protein co-phase separation, showing that charge patterning influences RNA incorporation and condensate structure.