Search

Your search keyword '"Chen, Shugui"' showing total 28 results
Start Over Author "Chen, Shugui"
28 results on '"Chen, Shugui"'

2. Structure and Functional Characterization of a Humanized Anti-CCL20 Antibody following Exposure to Serum Reveals the Formation of Immune Complex That Leads to Toxicity

Author

Thomson, Andrew S., primary, Mai, Shing H., additional, Bouma, Gerben, additional, Herdman, Michael, additional, Byrne, Michael, additional, Hottenstein, Charles S., additional, Minetti, Joseph, additional, Trulli, Stephen, additional, Taylor, J. David, additional, White, John R., additional, and Chen, Shugui, additional

Published
2021
Full Text
View/download PDF

3. Immune complex disease in a chronic monkey study with a humanised, therapeutic antibody against CCL20 is associated with complement-containing drug aggregates

Author

Laffan, Susan B., primary, Thomson, Andrew S., additional, Mai, Shing, additional, Fishman, Cindy, additional, Kambara, Takahito, additional, Nistala, Kiran, additional, Raymond, James T., additional, Chen, Shugui, additional, Ramani, Thulasi, additional, Pageon, Laura, additional, Polsky, Rodd, additional, Watkins, Mark, additional, Ottolangui, Gemma, additional, White, John R., additional, Maier, Curtis, additional, Herdman, Michael, additional, and Bouma, Gerben, additional

Published
2020
Full Text
View/download PDF

4. Artificial strain of human prions created in vitro

Author

Kim, Chae, primary, Xiao, Xiangzhu, additional, Chen, Shugui, additional, Haldiman, Tracy, additional, Smirnovas, Vitautas, additional, Kofskey, Diane, additional, Warren, Miriam, additional, Surewicz, Krystyna, additional, Maurer, Nicholas R., additional, Kong, Qingzhong, additional, Surewicz, Witold, additional, and Safar, Jiri G., additional

Published
2018
Full Text
View/download PDF

6. Interaction between Human Prion Protein and Amyloid-β (Aβ) Oligomers: ROLE OF N-TERMINAL RESIDUES*

Author

Chen, Shugui, Yadav, Satya P., and Surewicz, Witold K.

Subjects
Amyloid beta-Peptides, Binding Sites, Polymorphism, Genetic, Alzheimer Disease, Prions, Protein Structure and Folding, Humans, PrPC Proteins, Spin Labels, Surface Plasmon Resonance, Peptide Fragments, Protein Binding
Abstract

Soluble oligomers of Abeta42 peptide are believed to play a major role in the pathogenesis of Alzheimer disease (AD). It was recently found that at least some of the neurotoxic effects of these oligomers may be mediated by specific binding to the prion protein, PrP(C), on the cell surface (Laurén, J., Gimbel, D. A., Nygaard, H. B., Gilbert, J. W., and Strittmatter, S. M. (2009) Nature 457, 1128-1132). Here we characterized the interaction between synthetic Abeta42 oligomers and the recombinant human prion protein (PrP) using two biophysical techniques: site-directed spin labeling and surface plasmon resonance. Our data indicate that this binding is highly specific for a particular conformation adopted by the peptide in soluble oligomeric species. The binding appears to be essentially identical for the Met(129) and Val(129) polymorphic forms of human PrP, suggesting that the role of PrP codon 129 polymorphism as a risk factor in AD is due to factors unrelated to the interaction with Abeta oligomers. It was also found that in addition to the previously identified approximately 95-110 segment, the second region of critical importance for the interaction with Abeta42 oligomers is a cluster of basic residues at the extreme N terminus of PrP (residues 23-27). The deletion of any of these segments results in a major loss of the binding function, indicating that these two regions likely act in concert to provide a high affinity binding site for Abeta42 oligomers. This insight may help explain the interplay between the postulated protective and pathogenic roles of PrP in AD and may contribute to the development of novel therapeutic strategies as well.

Published
2010

14. Abstract 2221: Enhanced SH3:linker interaction allosterically sensitizes Abl kinases to small molecule inhibitors

Author

Thomas E. Wales, Shoghag Panjarian, John R. Engen, Thomas E. Smithgall, Chen Shugui, and Roxana E. Iacob

Subjects
Cancer Research, ABL, Kinase, Chemistry, Small molecule, SH3 domain, Oncology, Biochemistry, Protein kinase domain, hemic and lymphatic diseases, Biophysics, Binding site, Kinase activity, Linker
Abstract

Bcr-Abl is the oncogenic protein-tyrosine kinase responsible for the pathogenesis of chronic myelogenous leukemia (CML). Clinical management of CML has been revolutionized by imatinib, a selective ATP-competitive inhibitor of Bcr-Abl kinase activity. Imatinib selectivity is due in part to its ability to recognize and stabilize the inactive conformation of the kinase domain. This conformation is stabilized by intramolecular binding of the SH3 domain to the SH2-kinase linker, which in turn packs against the back of the kinase domain. Imatinib resistance can be caused by point mutations that either affect drug binding directly (e.g., through mutation of the gatekeeper position, Thr315) or that allosterically disturb the downregulated kinase domain conformation (e.g., through mutation or phosphorylation of the SH3 domain). These observations suggest that strengthening the regulatory SH3:linker interaction present in Bcr-Abl may stabilize a downregulated kinase domain conformation, thus sensitizing the kinase domain to inhibitor action. To explore this possibility, we created a series of modified c-Abl and Bcr-Abl proteins with enhanced SH3-linker interactions. By systematically increasing the proline content of the linker, we identified high-affinity linkers that stabilized intramolecular SH3 binding without disturbing the overall regulation of the kinase core. Enhanced SH3:linker interaction completely reversed c-Abl core activation by a C-lobe myristate binding pocket mutation, and substantially reduced activation by mutations in the ATP binding site (T315I) as well as the SH2:C-lobe interface (Y158D). Remarkably, enhanced SH3:linker interaction dramatically sensitized Bcr-Abl not only to imatinib but also to the myristic acid binding pocket inhibitor, GNF-2. These effects were observed in the context of both wild-type and imatinib-resistant forms of Bcr-Abl. Hydrogen exchange mass spectrometry of recombinant Abl core proteins with high-affinity linkers revealed dynamic coupling between the SH3:linker interface, the GNF-2 binding site in the C-lobe myristate binding pocket, and the active site. Taken together, these studies provide strong evidence that regulatory SH3:linker interaction is retained in the context of Bcr-Abl, and supports the idea that small molecules enhancing natural regulatory interaction at the SH3:linker interface may have utility as chemical sensitizers of Bcr-Abl drug action in the kinase domain. Citation Format: Shoghag B. Panjarian, Roxana Iacob, Chen Shugui, Thomas Wales, John R. Engen, Thomas E. Smithgall. Enhanced SH3:linker interaction allosterically sensitizes Abl kinases to small molecule inhibitors. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 2221. doi:10.1158/1538-7445.AM2013-2221

Published
2013

16. Structural Polymorphism in Amyloids

Author

Jones, Eric M., primary, Wu, Bo, additional, Surewicz, Krystyna, additional, Nadaud, Philippe S., additional, Helmus, Jonathan J., additional, Chen, Shugui, additional, Jaroniec, Christopher P., additional, and Surewicz, Witold K., additional

Published
2011
Full Text
View/download PDF

20. Reply to Kascsak: Definition of the PrP 3F4 Epitope Revisited

Author

Zou, Wen-Quan, primary, Langeveld, Jan, additional, Xiao, Xiangzhu, additional, Chen, Shugui, additional, McGeer, Patrick L., additional, Yuan, Jue, additional, Payne, Michael C., additional, Kang, Hae-Eun, additional, McGeehan, John, additional, Sy, Man-Sun, additional, Greenspan, Neil S., additional, Kaplan, David, additional, Wang, Gong-Xian, additional, Parchi, Piero, additional, Hoover, Edward, additional, Kneale, Geoff, additional, Telling, Glenn, additional, Surewicz, Witold K., additional, Kong, Qingzhong, additional, and Guo, Jian-Ping, additional

Published
2010
Full Text
View/download PDF

21. PrP Conformational Transitions Alter Species Preference of a PrP-specific Antibody

Author

Zou, Wen-Quan, primary, Langeveld, Jan, additional, Xiao, Xiangzhu, additional, Chen, Shugui, additional, McGeer, Patrick L., additional, Yuan, Jue, additional, Payne, Michael C., additional, Kang, Hae-Eun, additional, McGeehan, John, additional, Sy, Man-Sun, additional, Greenspan, Neil S., additional, Kaplan, David, additional, Wang, Gong-Xian, additional, Parchi, Piero, additional, Hoover, Edward, additional, Kneale, Geoff, additional, Telling, Glenn, additional, Surewicz, Witold K., additional, Kong, Qingzhong, additional, and Guo, Jian-Ping, additional

Published
2010
Full Text
View/download PDF

26. Structural Determinants of Phenotypic Diversity and Replication Rate of Human Prions.

Author

Kabir, Mohammad E., Kim, Chae, Haldiman, Tracy, Safar, Jiri G., Cohen, Mark L., Cohen, Yvonne, Chen, Wei, Xiao, Xiangzhu, Chen, Shugui, and Surewicz, Witold K.

Subjects
PRION diseases, CREUTZFELDT-Jakob disease, REPLICATION factors (Biochemistry), PHENOTYPIC plasticity, CONFORMATIONAL analysis, DEUTERIUM
Abstract

The infectious pathogen responsible for prion diseases is the misfolded, aggregated form of the prion protein, PrPSc. In contrast to recent progress in studies of laboratory rodent-adapted prions, current understanding of the molecular basis of human prion diseases and, especially, their vast phenotypic diversity is very limited. Here, we have purified proteinase resistant PrPSc aggregates from two major phenotypes of sporadic Creutzfeldt-Jakob disease (sCJD), determined their conformational stability and replication tempo in vitro, as well as characterized structural organization using recently emerged approaches based on hydrogen/deuterium (H/D) exchange coupled with mass spectrometry. Our data clearly demonstrate that these phenotypically distant prions differ in a major way with regard to their structural organization, both at the level of the polypeptide backbone (as indicated by backbone amide H/D exchange data) as well as the quaternary packing arrangements (as indicated by H/D exchange kinetics for histidine side chains). Furthermore, these data indicate that, in contrast to previous observations on yeast and some murine prion strains, the replication rate of sCJD prions is primarily determined not by conformational stability but by specific structural features that control the growth rate of prion protein aggregates. [ABSTRACT FROM AUTHOR]

Published
2015
Full Text
View/download PDF

27. The Abl SH2-kinase linker naturally adopts a conformation competent for SH3 domain binding.

Author

Chen, Shugui, Brier, Sébastien, Smithgall, Thomas E., and Engen, John R.

Abstract

The core of the Abelson tyrosine kinase (c-Abl) is structurally similar to Src-family kinases where SH3 and SH2 domains pack against the backside of the kinase domain in the down-regulated conformation. Both kinase families depend upon intramolecular association of SH3 with the linker joining the SH2 and kinase domains for suppression of kinase activity. Hydrogen deuterium exchange (HX) and mass spectrometry (MS) were used to probe intramolecular interaction of the c-Abl SH3 domain with the linker in recombinant constructs lacking the kinase domain. Under physiological conditions, the c-Abl SH3 domain undergoes partial unfolding, which is stabilized by ligand binding, providing a unique assay for SH3:linker interaction in solution. Using this approach, we observed dynamic association of the SH3 domain with the linker in the absence of the kinase domain. Truncation of the linker before W254 completely prevented cis-interaction with SH3, while constructs containing amino acids past this point showed SH3:linker interactions. The observation that the Abl linker sequence exhibits SH3-binding activity in the absence of the kinase domain is unique to Abl and was not observed with Src-family kinases. These results suggest that SH3:linker interactions may have a more prominent role in Abl regulation than in Src kinases, where the down-regulated conformation is further stabilized by a second intramolecular interaction between the C-terminal tail and the SH2 domain. [ABSTRACT FROM AUTHOR]

Published
2007
Full Text
View/download PDF

28. Interaction between human prion protein and amyloid-beta (Abeta) oligomers: role OF N-terminal residues.

Author

Chen S, Yadav SP, and Surewicz WK

Subjects
Alzheimer Disease etiology, Amyloid beta-Peptides chemistry, Binding Sites, Humans, Peptide Fragments chemistry, Peptide Fragments metabolism, Polymorphism, Genetic, PrPC Proteins chemistry, PrPC Proteins genetics, Prions chemistry, Prions metabolism, Protein Binding, Spin Labels, Surface Plasmon Resonance, Amyloid beta-Peptides metabolism, PrPC Proteins metabolism
Abstract

Soluble oligomers of Abeta42 peptide are believed to play a major role in the pathogenesis of Alzheimer disease (AD). It was recently found that at least some of the neurotoxic effects of these oligomers may be mediated by specific binding to the prion protein, PrP(C), on the cell surface (Laurén, J., Gimbel, D. A., Nygaard, H. B., Gilbert, J. W., and Strittmatter, S. M. (2009) Nature 457, 1128-1132). Here we characterized the interaction between synthetic Abeta42 oligomers and the recombinant human prion protein (PrP) using two biophysical techniques: site-directed spin labeling and surface plasmon resonance. Our data indicate that this binding is highly specific for a particular conformation adopted by the peptide in soluble oligomeric species. The binding appears to be essentially identical for the Met(129) and Val(129) polymorphic forms of human PrP, suggesting that the role of PrP codon 129 polymorphism as a risk factor in AD is due to factors unrelated to the interaction with Abeta oligomers. It was also found that in addition to the previously identified approximately 95-110 segment, the second region of critical importance for the interaction with Abeta42 oligomers is a cluster of basic residues at the extreme N terminus of PrP (residues 23-27). The deletion of any of these segments results in a major loss of the binding function, indicating that these two regions likely act in concert to provide a high affinity binding site for Abeta42 oligomers. This insight may help explain the interplay between the postulated protective and pathogenic roles of PrP in AD and may contribute to the development of novel therapeutic strategies as well.

Published
2010
Full Text
View/download PDF

Catalog

Books, media, physical & digital resources
See catalog results