Biology subjects

Chung, Y. K.

Publications and source records attributed to Chung, Y. K..

3 recordsLinked to original sources

bioRxiv2026

Direct tensile force activates Adgrl3 in a tethered agonist-dependent manner

Adhesion G protein-coupled receptors are proposed to function as mechanosensors, yet whether controlled mechanical force can directly activate receptor signaling in living cells remains unclear. Using optical tweezers, we demonstrate that direct tensile force applied to the N-terminus of the adhesion GPCR Adgrl3 is sufficient to induce G protein recruitment in living cells. Activation is direction-specific, requires a functional tethered agonist, and aligns with coexisting force-driven GAIN-domain conformational changes and dissociation.

cell biology↗

bioRxiv2024

Quantum-classical hybrid approach for codon optimizationand its practical applications

Codon optimization is crucial for gene expression in heterologous hosts with varying genetic codes and codon usage, potentially resulting in enhanced protein expression and stability. Traditionally, the codon optimization problem has been solved using classical numerical techniques; however, with recent advancements, quantum algorithms deployed on quantum computers have been adopted for this purpose. This study proposes a codon sequence search protocol tailored to host preferences. Specifically, codon optimization is formulated as a constrained quadratic binary problem and solved using a quantum-classical hybrid approach, integrating quantum annealing with the Lagrange multiplier method. The proposed methodology is then applied to two real-world scenarios: optimizing the codon sequence of the severe respiratory syndrome coronavirus 2 spike protein in human hosts and insulin in Escherichia coli (E. coli) hosts. Finally, evaluations of several biological metrics demonstrate the effectiveness of our protocol, offering insights into the codon usage patterns governing translational efficiency and adaptation to the genetic code preferences of the host organisms.

bioinformatics↗

bioRxiv2023

Structural basis of GAIN domain autoproteolysis and cleavage-resistance in the adhesion G-protein coupled receptors

The GAIN domain is a hallmark of adhesion G-protein coupled receptors (aGPCRs) as this extracellular domain contains an integral agonistic sequence (Stachel) for activation via binding to the 7-transmembrane helical (7TM) domain of the receptor. Many aGPCRs are autoproteolytically cleaved at the GPCR proteolysis site (GPS) site within the GAIN domain formed HXS/T sequence motif. However, other aGPCR can be activated without GPS cleavage. We determined the crystal structure of the human ADGRB2/BAI2 hormone receptor (HormR) and GPCR autoproteolysis-inducing (GAIN) domains and found that this aGPCR is resistant to autoproteolysis despite the presence of a canonical HLS sequence motif at the GPS. We used structural comparisons and molecular dynamics (MD) simulations to identify structural determinants that are important for autocleavage beyond the canonical HXS/T motif. These studies characterized a conserved glycine residue and an edge-{pi} interaction of the histidine base of the GPS sequence with a phenylalanine residue that is highly conserved in cleavage-competent aGPCRs. The MD simulations showed that this interaction is important to position the imidazole group of the histidine for deprotonation of the serine or threonine nucleophile. Removal of this interaction reduced autoprote-olytic activity in the ADGRL1 receptor and restored cleavage competence of the ADGRB3 receptor in a R866H/L821F double mutant. Conservation analysis indicates that wild-type ADGRB2 and ADGRB3 are auto-cleavage-incompetent receptors.

biochemistry↗