| 1. |
- Choi, Seong Il, et al.
(author)
-
A Conceptual Framework for Integrating Cellular Protein Folding, Misfolding and Aggregation
- 2021
-
In: Life. - : MDPI AG. - 2075-1729. ; 11:7
-
Research review (peer-reviewed)abstract
- How proteins properly fold and maintain solubility at the risk of misfolding and aggregation in the cellular environments still remains largely unknown. Aggregation has been traditionally treated as a consequence of protein folding (or misfolding). Notably, however, aggregation can be generally inhibited by affecting the intermolecular interactions leading to aggregation, independently of protein folding and conformation. We here point out that rigorous distinction between protein folding and aggregation as two independent processes is necessary to reconcile and underlie all observations regarding the combined cellular protein folding and aggregation. So far, the direct attractive interactions (e.g., hydrophobic interactions) between cellular macromolecules including chaperones and interacting polypeptides have been widely believed to mainly stabilize polypeptides against aggregation. However, the intermolecular repulsions by large excluded volume and surface charges of cellular macromolecules can play a key role in stabilizing their physically connected polypeptides against aggregation, irrespective of the connection types and induced conformational changes, underlying the generic intrinsic chaperone activity of cellular macromolecules. Such rigorous distinction and intermolecular repulsive force-driven aggregation inhibition by cellular macromolecules could give new insights into understanding the complex cellular protein landscapes that remain uncharted.
|
|
| 2. |
- Choi, Seong Il, et al.
(author)
-
A social distancing measure governing the whole proteome
- 2021
-
In: Current opinion in structural biology. - : Elsevier BV. - 0959-440X .- 1879-033X. ; 66, s. 104-111
-
Journal article (peer-reviewed)abstract
- Protein folding in vivo has been largely understood in the context of molecular chaperones preventing aggregation of nascent polypeptides in the crowded cellular environment. Nascent chains utilize the crowded environment in favor of productive folding by direct physical connection with cellular macromolecules. The intermolecular repulsive forces by large excluded volume and surface charges of interacting cellular macromolecules, exerting ‘social distancing’ measure among folding intermediates, could play an important role in stabilizing their physically connected polypeptides against aggregation regardless of the physical connection types. The generic intrinsic chaperone activity of cellular macromolecules likely provides a robust cellular environment for the productive protein folding and solubility maintenance at the whole proteome level.
|
|
| 3. |
- Kim, Young-Seok, et al.
(author)
-
Built-in RNA-mediated chaperone (chaperna) for antigen folding tailored to immunized hosts
- 2020
-
In: Biotechnology and Bioengineering. - : Wiley. - 0006-3592 .- 1097-0290. ; 117:7, s. 1990-2007
-
Journal article (peer-reviewed)abstract
- High-quality antibody (Ab) production depends on the availability of immunologically relevant antigens. We present a potentially universal platform for generating soluble antigens from bacterial hosts, tailored to immunized animals for Ab production. A novel RNA-dependent chaperone, in which the target antigen is genetically fused with an RNA-interacting domain (RID) docking tag derived from the immunized host, promotes the solubility and robust folding of the target antigen. We selected the N-terminal tRNA-binding domain of lysyl-tRNA synthetase (LysRS) as the RID for fusion with viral proteins and demonstrated the expression of the RID fusion proteins in their soluble and native conformations; immunization predominantly elicited Ab responses to the target antigen, whereas the self RID tag remained nonimmunogenic. Differential immunogenicity of the fusion proteins greatly enriched and simplified the screening of hybridoma clones of monoclonal antibodies (mAbs), enabling specific and sensitive serodiagnosis of MERS-CoV infection. Moreover, mAbs against the consensus influenza hemagglutinin stalk domain enabled a novel assay for trivalent seasonal influenza vaccines. The Fc-mediated effector function was demonstrated, which could be harnessed for the design of next-generation universal influenza vaccines. The nonimmunogenic built-in antigen folding module tailored to a repertoire of immunized animal hosts will drive immunochemical diagnostics, therapeutics, and designer vaccines.
|
|
