Biology subjects

Jang, S.-Y.

Publications and source records attributed to Jang, S.-Y..

3 recordsLinked to original sources

bioRxiv2026

Rational Redesign of an Fc-Binding Peptide for Multivalent Antibody Assembly

Multivalent antibody assemblies offer opportunities to enhance avidity, organize immune complexes, and modulate higher-order protein interactions, but constructing such architectures from existing immunoglobulin G (IgG) molecules without redesigning the antibody scaffold remains challenging. Here, we report the rational redesign of a Protein A-derived Fc-binding peptide into ADP1, a stable dimeric Fc-binding peptide that directs Fc-mediated antibody assembly. ADP1 was designed from the parent Fc-binding peptide Z34C by preserving the Fc-recognition surface while redesigning the opposite helical surface to promote peptide-peptide association. Biophysical characterization showed that ADP1 retained nanomolar Fc-binding affinity while exhibiting markedly enhanced chemical and proteolytic stability compared with the parent peptide. Structural analyses of ADP1-Fc complexes revealed that ADP1 bridges neighboring Fc regions through a combined ADP1-Fc and ADP1-ADP1 interface, generating spiral higher-order Fc assemblies. This assembly principle was further extended to full-length IgG, where ADP1 promoted higher-order antibody association in a concentration-sensitive manner. In addition, covalent ADP1 functionalization enabled Fc-directed modification of full-length IgG while retaining Fab-mediated antigen recognition, demonstrating the utility of ADP1 as an antibody assembly and functionalization module. Finally, competitive addition of the parent Z34C peptide modulated ADP1-driven antibody assembly, suggesting a potential route for tuning Fc-mediated assembly propagation. Together, this work establishes a redesigned Fc-binding peptide platform for directing multivalent antibody assembly and functionalization without genetic reengineering of the IgG scaffold. Graphical abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=177 SRC="FIGDIR/small/737354v2_ufig1.gif" ALT="Figure 1"> View larger version (42K): org.highwire.dtl.DTLVardef@57cadeorg.highwire.dtl.DTLVardef@1c7d8e6org.highwire.dtl.DTLVardef@170fb85org.highwire.dtl.DTLVardef@90e6d6_HPS_FORMAT_FIGEXP M_FIG C_FIG

biochemistry↗

bioRxiv2024

HSP90 interacts with VP37 to facilitate the cell-to-cell movement of broad bean wilt virus 2

The systemic spread of viruses in plants requires successful viral cell-to-cell movement through plasmodesmata (PD). Viral movement proteins (MPs) interact with cellular proteins to modify and utilize host transport routes. Broad bean wilt virus 2 (BBWV2), a widespread plant RNA virus, moves from cell to cell as a virion through the PD gated by VP37, the MP of BBWV2. However, the host proteins that function in the cell-to-cell movement of BBWV2 remain unclear. In this study, we identified cellular heat shock protein 90 (HSP90) as an interacting partner of VP37. The interaction between HSP90 and VP37 was assessed using the yeast two-hybrid assay, co-immunoprecipitation, and bimolecular fluorescence complementation. Tobacco rattle virus-based virus-induced gene silencing analysis revealed that HSP90 silencing significantly inhibited the systemic spread of BBWV2 in N. benthamiana plants. Furthermore, in planta treatment with geldanamycin (GDA), an inhibitor of the chaperone function of HSP90, demonstrated the necessity of HSP90 in successful cell-to-cell movement and systemic infection of BBWV2. Interestingly, GDA treatment inhibited the HSP90-VP37 interaction at the PD, resulting in the inhibition of VP37-derived tubule formation through the PD. Our results suggest that the HSP90-VP37 interaction regulates VP37-derived tubule formation through the PD, thereby facilitating the cell-to-cell movement of BBWV2. IMPORTANCEThis study highlights the regulatory role of heat shock protein 90 (HSP90) in facilitating the cell-to-cell movement of broad bean wilt virus 2 (BBWV2). HSP90 interacted with VP37, the movement protein of BBWV2, specifically at plasmodesmata (PD). This study demonstrated that the HSP90-VP37 interaction is crucial for viral cell-to-cell movement and the formation of VP37-derived tubules, which are essential structures for virus transport through the PD. The ATP-dependent chaperone activity of HSP90 is integral to this interaction, as demonstrated by the inhibition of virus movement upon treatment with geldanamycin (GDA), which disrupts the function of HSP90. These findings elucidate the molecular mechanisms underlying the cell-to-cell movement of plant viruses, and highlight the role of HSP90 in viral infection. This study suggests that the chaperone activity of HSP90 may function in changing the conformational structure of VP37, thereby facilitating the assembly and function of virus-induced structures required for viral cell-to-cell movement.

microbiology↗

bioRxiv2023

Discrete projections from MCH neurons mediate anti-parkinsonian effects of acupuncture

Parkinsons disease (PD) presents with typical motor dysfunction and non-motor symptoms, including memory loss. Although acupuncture is suggested as an alternative therapy for PD, its neuroanatomical mechanisms remain unclear. We demonstrate that acupuncture ameliorates both motor and memory deficits in PD mice through activation of melanin-concentrating hormone (MCH) neurons in the lateral hypothalamus and zona incerta (LH/ZI)--MCHLH/ZI-- via nerve conduction. We identify two distinct subpopulations of MCHLH/ZI projecting to the substantia nigra and hippocampus, each of which is responsible for controlling motor and memory function. This effect can be attributed to MCH-mediated recovery from dopaminergic neurodegeneration, reactive gliosis, and impaired hippocampal synaptic plasticity. Collectively, MCHLH/ZI constitutes not only the neuroanatomical basis of acupuncture but also a potential cellular target for treating both motor and non-motor PD symptoms. One-Sentence SummaryAcupuncture alleviates both motor and non-motor symptoms in Parkinsons disease by activating two distinct MCH projections.

neuroscience↗