Article
Biochemistry & Molecular Biology
Jaime Santos, Irantzu Pallares, Valentin Iglesias, Salvador Ventura
Summary: The prevalence of cryptic amyloidogenic regions (CARs) of polar nature in intrinsically disordered regions (IDRs) has been explored. CARs are associated with protein function and interactions, but also carry a risk of malfunction. The existence of ancestral CARs may have evolved into functional interacting regions, playing a significant role in protein evolution at the origins of life.
COMPUTATIONAL AND STRUCTURAL BIOTECHNOLOGY JOURNAL
(2021)
Article
Biochemistry & Molecular Biology
Julien Mignon, Denis Mottet, Tanguy Leyder, Vladimir N. Uversky, Eric A. Perpete, Catherine Michaux
Summary: This study thoroughly characterized the structural properties and aggregation behavior of DPF3a and DPF3b isoforms. It was found that DPF3a is more disordered and exhibits more expanded conformations compared to DPF3b. Both isoforms can aggregate into amyloid fibrils, but DPF3a fibrillates at a faster rate.
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
(2022)
Article
Biochemistry & Molecular Biology
Carlos Pintado-Grima, Oriol Barcenas, Zoe Manglano-Artunedo, Rita Vilaca, Sandra Macedo-Ribeiro, Irantzu Pallares, Jaime Santos, Salvador Ventura
Summary: Proteome-wide analyses have revealed that amyloidogenic regions are present in most globular proteins, while being underrepresented in intrinsically disordered proteins (IDPs). However, recent research has shown that intrinsically disordered regions (IDRs) do contain significant amyloid load in the form of cryptic amyloidogenic regions (CARs), which are exposed to solvent and are more polar than conventional amyloid regions. CARs are associated with both IDPs function and malfunction, and their presence is linked to pathologies such as cancer and Alzheimer's disease. To explore these previously unnoticed amyloidogenic regions, CARs-DB, a database containing precomputed predictions for all CARs in the IDPs deposited in the DisProt database, was developed. CARs-DB allows for easy access to a large number of unique CARs and has been validated by demonstrating the amyloidogenic potential of selected CARs.
FRONTIERS IN MOLECULAR BIOSCIENCES
(2022)
Review
Biochemistry & Molecular Biology
Rakesh Trivedi, Hampapathalu Adimurthy Nagarajaram
Summary: This review discusses different aspects of disordered proteins and protein regions, as well as the experimental and computational methods used to characterize them. Additionally, the role of disordered proteins in diseases and their potential as drug targets are explored.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Microbiology
S. P. Venkata Subbaiah, Patil Pranita Uttamrao, Uttam Das, Sruthi Sundaresan, Thenmalarchelvi Rathinavelan
Summary: Saccharomyces cerevisiae Stm1 protein plays an important role in ribosome preservation and apoptosis-like cell death. It can recognize specific DNA structures and its conformation and fibrillation are influenced by protein concentration and salt concentration.
FRONTIERS IN MICROBIOLOGY
(2023)
Article
Polymer Science
Min-Kyung Chae, Nam-Kyung Lee, Youngkyun Jung, Albert Johner
Summary: Charged polymers with random charge sequences form pearl-necklace structures, with dynamics of pearls controlled by nucleation/dissolution processes. Most sequences have a stable number of large pearls, while a few exhibit fast-switching behavior. Similar shape fluctuations are observed in intrinsically disordered protein (IDP) sequences.
Article
Biochemistry & Molecular Biology
Katharina Laass, Felipe Garcia Quiroz, Johannes Hunold, Stefan Roberts, Ashutosh Chilkoti, Dariush Hinderberger
Summary: The study reveals the hydration dynamics in phase-separating IDPs, showing that side-chain rehydration forms a dynamic water shield that affects solubility. This water shell strength is a sequence feature of IDPs, encoding for the stability of their phase-separated assemblies. The complexity of nanoscopic water-IDP interactions dictates their rich phase separation behavior.
Article
Chemistry, Physical
Priyanka Dogra, Shruti Arya, Avinash K. Singh, Anindya Datta, Samrat Mukhopadhyay
Summary: The conformational plasticity of intrinsically disordered proteins (IDPs) is important for their biological functions, and is governed by chain-chain and chain-solvent interactions. In this study, the conformational and solvation dynamics around the N and C-terminal segments of a protein called Pmel17, which forms functional amyloid responsible for melanin biosynthesis, were characterized using fluorescence measurements. The results showed slight compaction and slower rotational dynamics around the amyloidogenic C-terminal segment compared to the proline-rich N-terminal segment. This compaction was associated with restrained mobility of hydration water. These findings highlight the importance of sequence-dependent chain-solvent interactions in directing the conversion of dynamic IDPs into ordered amyloid assemblies.
JOURNAL OF PHYSICAL CHEMISTRY B
(2022)
Review
Biochemistry & Molecular Biology
H. Jane Dyson
Summary: Viruses infect all kingdoms of life and employ disordered proteins to accomplish various functions. Disordered proteins have been discovered in almost all viruses studied, regardless of the viral genome composition or the viral capsid configuration. This review presents a collection of stories illustrating the diverse functions of disordered proteins in viruses, providing a survey of the field's expansion.
JOURNAL OF MOLECULAR BIOLOGY
(2023)
Article
Chemistry, Physical
Hiranmay Maity, Lipika Baidya, Govardhan Reddy
Summary: Salts play a role in modulating the behavior of intrinsically disordered proteins (IDPs) through liquid-liquid phase separation (LLPS). In low ionic strength solutions, the behavior of IDPs can be explained using the theory for salt-induced transitions in charged polymers. However, in high ionic strength solutions, the specific interactions between salts and charged/uncharged residues, known as the Hofmeister effect, influence the behavior of IDPs. The study proposes a simulation methodology to study salt-specific transitions in IDPs by using a coarse-grained IDP model and experimentally measured water to salt solution transfer free energies.
JOURNAL OF PHYSICAL CHEMISTRY B
(2022)
Article
Nanoscience & Nanotechnology
Xiangze Zeng, Chengwen Liu, Martin J. Fossat, Pengyu Ren, Ashutosh Chilkoti, Rohit Pappu
Summary: This study discusses the characteristics of naturally occurring elastomers and their phase behavior at LCST and UCST, finding that control over LCST phase behavior can be achieved through sequence design. By utilizing methods such as Monte Carlo simulations, genetic algorithms, and the ABSINTH model, novel sequences with LCST phase behavior are successfully designed.
Review
Chemistry, Multidisciplinary
Matti Mar, Kateryna Nitsenko, Petur O. Heidarsson
Summary: Eukaryotic transcription factors play a crucial role in integrating molecular feedback and regulating gene expression. They consist of structured DNA-binding domains and long intrinsically disordered regions (IDRs). The dynamic multifunctionality of IDRs is essential for their functions in genome regulation. This review analyzes the chemical features of TF IDRs and their involvement in protein interactions, DNA binding, chromatin opening, and phase separation. Suggestions are given for future research to integrate experiments and simulations in understanding TF functions.
CHEMISTRY-A EUROPEAN JOURNAL
(2023)
Article
Biochemistry & Molecular Biology
Tanguy Leyder, Julien Mignon, Denis Mottet, Catherine Michaux
Summary: This study investigated the disorder aggregation properties of the C-terminal isoforms of double-PHD fingers 3 (DPF3) and found that they can spontaneously assemble into beta-sheet-rich fibrils. The study also assessed the influence of divalent metal cations on the aggregation pathway and found that different metal cations have varying effects on the aggregation and structure of the C-terminal isoforms.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Biochemistry & Molecular Biology
Vladimir D. Manyilov, Nikolay S. Ilyinsky, Semen V. Nesterov, Baraa M. G. A. Saqr, Guy W. Dayhoff, Egor V. Zinovev, Simon S. Matrenok, Alexander V. Fonin, Irina M. Kuznetsova, Konstantin K. Turoverov, Valentin Ivanovich, Vladimir N. Uversky
Summary: This article examines the impact of intrinsically disordered proteins and regions on aging-related processes. The findings indicate that these disordered components play significant roles in aging, particularly in genome regulation.
CELLULAR AND MOLECULAR LIFE SCIENCES
(2023)
Article
Chemistry, Medicinal
Souvik Mondal, Krishna Prasad Ghanta, Sanjoy Bandyopadhyay
Summary: This study investigates the dynamic properties of water near the α-synuclein protein associated with Parkinson's disease. The results show that the translational and rotational mobility of water molecules near the peptide segments are significantly restricted, with water near the hydrophobic segment exhibiting more restricted diffusivity. The time scales of peptide-water and water-water hydrogen bond relaxations correlate with the diffusion of interfacial water molecules. The hindered dynamic environment near a specific segment can enhance early stages of peptide aggregation.
JOURNAL OF CHEMICAL INFORMATION AND MODELING
(2022)
Article
Chemistry, Physical
Priyanka Dogra, Shruti Arya, Avinash K. Singh, Anindya Datta, Samrat Mukhopadhyay
Summary: The conformational plasticity of intrinsically disordered proteins (IDPs) is important for their biological functions, and is governed by chain-chain and chain-solvent interactions. In this study, the conformational and solvation dynamics around the N and C-terminal segments of a protein called Pmel17, which forms functional amyloid responsible for melanin biosynthesis, were characterized using fluorescence measurements. The results showed slight compaction and slower rotational dynamics around the amyloidogenic C-terminal segment compared to the proline-rich N-terminal segment. This compaction was associated with restrained mobility of hydration water. These findings highlight the importance of sequence-dependent chain-solvent interactions in directing the conversion of dynamic IDPs into ordered amyloid assemblies.
JOURNAL OF PHYSICAL CHEMISTRY B
(2022)
Article
Chemistry, Multidisciplinary
Debapriya Das, Lisha Arora, Samrat Mukhopadhyay
Summary: Protein folding and dynamics are influenced by thermal and viscosity-mediated effects, with internal friction playing a crucial role. The study demonstrates that sequence-specific backbone dihedral barriers control local internal friction in proteins, with different amino acid sequences affecting the level of internal friction.
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
(2022)
Article
Biochemistry & Molecular Biology
Sayanta Mahapatra, Anusha Sarbahi, Priyanka Madhu, Hema M. Swasthi, Abhishek Sharma, Priyanka Singh, Samrat Mukhopadhyay
Summary: This study investigates the role of substoichiometric Hsp104 in the formation and persistence of prefibrillar amyloid seeds. The results show that Hsp104 accelerates the formation of prefibrillar species and prolongs their persistence. In addition, Hsp104-modulated amyloid species have better seeding capability and exhibit distinct structural and dynamical characteristics compared to NM-only amyloids.
JOURNAL OF BIOLOGICAL CHEMISTRY
(2022)
Article
Multidisciplinary Sciences
Anamika Avni, Ashish Joshi, Anuja Walimbe, Swastik G. Pattanashetty, Samrat Mukhopadhyay
Summary: The authors introduced a unique single-droplet surface-enhanced Raman scattering (SERS) methodology to investigate molecular information within the mesoscopic liquid condensed phase. This study sheds light on the formation and regulation mechanism of biomolecular condensates. The highly sensitive measurements enable the capture of crucial interactions, conformational heterogeneity, and structural distributions.
NATURE COMMUNICATIONS
(2022)
Article
Microbiology
Lauren K. Nicastro, Jaime de Anda, Neha Jain, Kaitlyn C. M. Grando, Amanda L. Miller, Shingo Bessho, Stefania Gallucci, Gerard C. L. Wong, Cagla Tukel
Summary: Deposition of human amyloids is associated with complex human diseases such as Alzheimer's and Parkinson's. Amyloid proteins are also produced by bacteria, and the bacterial amyloid curli, when forming complexes with extracellular DNA, can trigger an autoimmune response in the host immune system. Different stages of curli fibrils formed during biofilm development have varying structural and pathogenic properties, with mature curli fibrils being the most pathogenic.
News Item
Biophysics
Sandeep K. Rai, Samrat Mukhopadhyay
BIOPHYSICAL JOURNAL
(2022)
Review
Chemistry, Multidisciplinary
Debapriya Das, Samrat Mukhopadhyay
Summary: Protein folding and dynamics are influenced by both thermal and viscosity effects, including external viscous drag from solvent molecules and internal friction within the polypeptide chain. The physical origin of internal friction in intrinsically disordered proteins remains unclear, with diffusive conformational dynamics dominated by segmental motion of the backbone. Polymer models with internal friction are used to describe the friction in complex biopolymeric systems such as intrinsically disordered proteins.
ACCOUNTS OF CHEMICAL RESEARCH
(2022)
Editorial Material
Biochemistry & Molecular Biology
Samrat Mukhopadhyay
Summary: Intrinsically disordered proteins (IDPs) are a class of proteins that expand the functional repertoire and are associated with various biological functions and human diseases. This thematic issue provides current trends and contemporary views on the unique structural and dynamical characteristics of these proteins, as well as their misfolding behavior, aggregation behavior, and phase transitions into biomolecular condensates.
ESSAYS IN BIOCHEMISTRY
(2022)
Article
Multidisciplinary Sciences
Sandeep K. Rai, Roopali Khanna, Anamika Avni, Samrat Mukhopadhyay
Summary: Biomolecular condensates formed through phase separation play crucial roles in cellular functions and disease. In this study, we investigate the complex coacervation of neuronal proteins tau and prion, driven by specific electrostatic interactions and characterized by dynamic liquid-like droplets. We employ a combination of time-resolved tools to reveal the formation of heterotypic condensates with domain-specific electrostatic nanoclusters. These condensates can be modulated by RNA, resulting in reversible, multiphasic ternary condensates of different morphologies. Aging leads to the conversion of droplets into solid-like co-assemblies, accompanied by the formation of amorphous and amyloid-like co-aggregates. Our findings provide mechanistic insights into the role of tau and PrP in neuropathology and highlight the broader biological significance of complex phase transitions.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2023)
Article
Biochemistry & Molecular Biology
Sayanta Mahapatra, Anusha Sarbahi, Neha Punia, Ashish Joshi, Anamika Avni, Anuja Walimbe, Samrat Mukhopadhyay
Summary: Prion-like self-perpetuating conformational conversion of proteins into amyloid aggregates is influenced by ATP molecules, which can both accelerate aggregation and disaggregate preformed fibrils. ATP modulates the formation and dissolution of amyloids and restricts autocatalytic amplification by controlling the amount of fragmentable and seeding-competent aggregates. Furthermore, ATP can promote phase separation-mediated aggregation of proteins harboring prion-like domains. These findings provide important mechanistic insights into the concentration-dependent chemical chaperoning by ATP against prion-like transmissions of amyloids.
JOURNAL OF BIOLOGICAL CHEMISTRY
(2023)
Article
Biochemistry & Molecular Biology
Archit Gupta, Ashish Joshi, Kanika Arora, Samrat Mukhopadhyay, Purnananda Guptasarma
Summary: The bacterial chromosome, known as its nucleoid, is an amorphous assemblage of globular nucleoprotein domains that exist as an irregularly-shaped, membrane-less, intracellular compartment separated from the cell's cytoplasm. Two abundant nucleoid-associated proteins, HU and Dps, undergo spontaneous complex coacervation with different forms of DNA/RNA, causing condensation and compaction of nucleic acids into liquid-liquid phase separated condensates in vitro. These complex coacervation modes may serve as models for understanding the in vivo relationships among nucleoid-associated proteins, explaining the presence of multiple isoforms of HU and the roles of HU and Dps in E. coli growth.
JOURNAL OF BIOLOGICAL CHEMISTRY
(2023)
Article
Chemistry, Physical
Anamika Avni, Ashish Joshi, Samrat Mukhopadhyay
Summary: Vibrational Raman spectroscopy coupled with hydrogen/deuterium exchange can discern key structural features responsible for diverse amyloid polymorphs. This noninvasive and label-free method allows for the structural differentiation of distinct amyloid polymorphs, capturing conformational heterogeneity and structural distributions. This research provides insights into the molecular factors governing structural diversity in amyloid polymorphs and could potentially simplify the study of amyloid remodeling by small molecules.
JOURNAL OF PHYSICAL CHEMISTRY LETTERS
(2023)
Article
Chemistry, Multidisciplinary
Antony Vincy, Yohan Gaikwad, Harshita Agarwal, Neha Jain, Raviraj Vankayala
Summary: In this study, a paper-based colorimetric dipstick sensor based on the principle of Prussian blue synthesis was developed for highly sensitive and rapid detection of bacterial contamination. The sensor is easy to fabricate and can detect bacteria up to 10(1) CFU/mL within minutes.
Article
Chemistry, Multidisciplinary
Rahul Kumar, Antony Vincy, Khushboo Rani, Neha Jain, Sarvar Singh, Ajay Agarwal, Raviraj Vankayala
Summary: This article presents an environmentally friendly method for the synthesis of highly luminescent carbon dots derived from camel milk, which can be used for sensing manganese ions and identifying potential anticancer activity against alpha-synuclein amyloids.
Article
Chemistry, Multidisciplinary
Rahul Kumar, Antony Vincy, Khushboo Rani, Neha Jain, Sarvar Singh, Ajay Agarwal, Raviraj Vankayala
Summary: In this study, highly luminescent carbon dots derived from camel milk were synthesized and used for sensing manganese ions and identifying their anticancer potential and antiamyloid activity. The carbon dots exhibited good water dispersibility, stable fluorescence, and excellent photostability, making them suitable for various biomedical applications.