Biology subjects

Son, A.

Publications and source records attributed to Son, A..

22 records · Page 2Linked to original sources

bioRxiv2022

Why are G-quadruplexes good at preventing protein aggregation?

Maintaining a healthy protein folding environment is essential for cellular function. Recently, we found that nucleic acids, and G-quadruplexes in particular, are potent chaperones for preventing protein aggregation. With the aid of structure-function and NMR analyses of two G-quadruplex forming sequences, PARP-I and LTR-III, we uncovered several contributing factors that affect G-quadruplexes in preventing protein aggregation. Notably, three factors emerged as vital in determining holdase activity of G-quadruplexes: their structural topology, structural dynamics, and oligomerization state. These factors together appear to largely dictate whether a G-quadruplex is able to prevent partially misfolded proteins from aggregating. Understanding the genesis of G-quadruplexes power as chaperones is an important facet to elucidating various protein aggregation diseases. Key Points- How nucleic acids act as protein chaperones is currently unknown. - G-quadruplexes are excellent at preventing protein aggregation, and here we describe basic tenets of this activity. - This activity could help design treatments for multiple neurodegenerative diseases.

biophysics↗

bioRxiv2021

Foldamers Reveal and Validate Novel Therapeutic Targets Associated with Toxic α-Synuclein Self-Assembly

Parkinsons disease (PD) is a progressive neurodegenerative disorder for which there is no successful prevention or intervention. The pathological hallmark for PD involves the self-assembly of functional Alpha-Synuclein (S) into non-functional amyloid structures. One of the potential therapeutic interventions against PD is the effective inhibition of S aggregation. However, the bottleneck towards achieving this goal is the identification of S domains/sequences that are essential for aggregation. Using a protein mimetic approach, we have identified S sequences-based novel targets that are essential for aggregation and will have significant therapeutic implications. An extensive array of in vitro, ex vivo, and in vivo assays was utilized to validate S sequences and their structural characteristics that are essential for aggregation and propagation of PD phenotypes. The study aids in developing significant mechanistic and therapeutic insights into various facets of S aggregation, which will pave the way for novel and effective treatments for PD.

biochemistry↗

bioRxiv2020

The SARS-CoV-2 RNA interactome

SARS-CoV-2 is an RNA virus whose success as a pathogen relies on its ability to repurpose host RNA-binding proteins (RBPs) to form its own RNA interactome. Here, we developed and applied a robust ribonucleoprotein capture protocol to uncover the SARS-CoV-2 RNA interactome. We report 109 host factors that directly bind to SARS-CoV-2 RNAs including general antiviral factors such as ZC3HAV1, TRIM25, and PARP12. Applying RNP capture on another coronavirus HCoV-OC43 revealed evolutionarily conserved interactions between viral RNAs and host proteins. Network and transcriptome analyses delineated antiviral RBPs stimulated by JAK-STAT signaling and proviral RBPs responsible for hijacking multiple steps of the mRNA life cycle. By knockdown experiments, we further found that these viral-RNA-interacting RBPs act against or in favor of SARS-CoV-2. Overall, this study provides a comprehensive list of RBPs regulating coronaviral replication and opens new avenues for therapeutic interventions.

microbiology↗

bioRxiv2018

Conversion of a soluble protein into a potent chaperone in vivo

Protein-folding assistance and aggregation inhibition by cellular factors are largely understood in the context of molecular chaperones. As an alternative and complementary model, we previously proposed that, in general, soluble cellular macromolecules including chaperones with large excluded volume and surface charges exhibit the intrinsic chaperone activity to prevent aggregation of their connected polypeptides, irrespective of the connection types, and thus to aid productive protein folding. As a proof of concept, we here demonstrated that a model soluble protein with an inactive protease domain robustly exerted chaperone activity toward various proteins harboring a short protease-recognition tag of 7 residues in Escherichia coli. The chaperone activity of this protein was similar or even superior to that of representative E. coli chaperones in vivo. Furthermore, in vitro refolding experiments confirmed the in vivo results. Our findings revealed that a soluble protein exhibits the intrinsic chaperone activity, which is manifested, upon binding to aggregation-prone proteins. This study gives new insights into the ubiquitous chaperoning role of cellular macromolecules in protein-folding assistance and aggregation inhibition underlying the maintenance of protein solubility and proteostasis in vivo.

biochemistry↗